Formation Of New Blood Vessels Research Articles

The past and future of angiogenesis as target for cancer therapy and prevention.

Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. Since this concept was established in the Seventies, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy and prevention and on substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, β-blockers, renin-angiotensin-aldosterone inhibitors, carnitines, and biguanides are reviewed.

The Potential Interplay Between HIF-1α, Angiogenic, and Autophagic Signaling During Intermittent Hypoxic Exposure and Exercise.

Berkemeier QN, Deyhle MR, McCormick JJ, Escobar KA, Mermier CM. The Potential Interplay between HIF-1α, Angiogenic, and Autophagic Signaling during Intermittent Hypoxic Exposure and Exercise High Alt Med Biol. 00:000-000, 2024.-Berkemeier QN, Deyhle MR, McCormick JJ, Escobar KA, Mermier CM. The Potential Interplay between HIF-1α, Angiogenic, and Autophagic Signaling During Intermittent Hypoxic Exposure and Exercise High Alt Med Biol. 00:000-000, 2024.-Environmental hypoxia as a result of decreased barometric pressure upon ascent to high altitudes (>2,500 m) presents increased physiological demands compared with low altitudes, or normoxic environments. Competitive athletes, mountaineers, wildland firefighters, military personnel, miners, and outdoor enthusiasts commonly participate in, or are exposed to, forms of exercise or physical labor at moderate to high altitudes. However, the majority of research on intermittent hypoxic exposure is centered around hematological markers, and the skeletal muscle cellular responses to exercise in hypoxic environments remain largely unknown. Two processes that may be integral for the maintenance of cellular health in skeletal muscle include angiogenesis, or the formation of new blood vessels from preexisting vasculature and autophagy, a process that removes and recycles damaged and dysfunctional cellular material in the lysosome. The purpose of this review is to is to examine the current body of literature and highlight the potential interplay between low-oxygen-sensing pathways, angiogenesis, and autophagy during acute and prolonged intermittent hypoxic exposure in conjunction with exercise.The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Army, DOD, DOE, ORAU/ORISE or U.S. Government.

Scaffold providing spatial guidance enhances the healing of osteochondral defects and reduce adverse bone-cartilage crosstalk

Despite previous attempts using multiphasic scaffolds to organize cells and bioactive elements, osteochondral repair still faces challenges, such as thin cartilage layers and uneven bone-cartilage interfaces. These issues are likely exacerbated by detrimental biochemical interactions and the formation of new blood vessels within the osteochondral unit, impacting tissue repair quality. In this study, we devised a novel freeze-welding technique to create a unified porous scaffold. Chitosan was chosen as the primary material due to its structural and compositional similarity to glycosaminoglycans in the ECM. In particular, by meticulously adjusting freezing and solute conditions, we engineered the scaffold to have an axially aligned porous structure in the cartilage layer and a radially aligned porous structure in the subchondral layer (scaffold A/R), each designed to meet the unique repair needs of the respective tissues. This scaffold showed enhanced mechanical compressibility, shape retention, and interfacial bonding capabilities. The results demonstrated that this unique spatial scaffold structure offers significant advantages over purely axial scaffolds in guiding osteochondral regeneration. These advantages were evident in its ability to independently promote cartilage and bone growth, reduce undesirable bone-cartilage crosstalk, particularly in the context of vessel invasion in the cartilage layer, and optimize the remodeling of the osteochondral interface. This study offers valuable insights into the structural design patterns for osteochondral regeneration, highlighting the potential importance of structural scaffold design in guiding endogenous tissue remodeling during heterogeneous tissue regeneration.

Abstract PO1-18-11: Imaging of tumour microvasculature using high-resolution contrast enhanced ultrasound together with markers of proliferation/angiogenesis/vascular mimicry to characterise response to NACT in TNBC

Abstract Background: In the UK, triple-negative breast cancer (TNBC) comprises 10-15% of breast cancer diagnoses annually. TNBC represents a clinical challenge due to a lack of expression of three treatable drug targets, namely oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER-2). The mainstay of treatment involves the use of neoadjuvant chemotherapy (NACT) followed by surgical excision where up to 50% of patients will achieve a pathological complete response (pCR). The addition of neo-adjuvant immunotherapy may increase the pCR rate to 60%. The presence of lymphatics and blood vessels within/around malignant tumours plays a role in cancer progression as does the formation of new blood vessels (angiogenesis). The vascular endothelial growth factor (VEGF) family and their receptors (VEGFRs) play an important role in angiogenesis as well as promoting the growth and survival of cancer cells. VEGFR is frequently overexpressed in TNBC and promotes changes in vascular endothelial cells, the basement membrane and the surrounding extracellular matrix. Co-expression of epidermal growth factor receptor (EGFR) and VEGFR enhances tumour growth and angiogenesis in an autocrine and paracrine manner. An alternate mechanism for tumour microcirculation in tumours is vasculogenic mimicry (VM). This is distinct from classical tumour angiogenesis. The presence of VM is associated with poor overall survival in breast cancer patients and anti-angiogenic treatment of TNBC may even promote tumour growth, proliferation and metastasis by stimulating VM. Conventional imaging techniques such as B-mode ultrasound and MRI are commonly used to monitor disease response in the breast but have limited accuracy in predicting pCR or residual disease. High-resolution contrast-enhanced ultrasound (HRCEUS) may offer a more accurate test to monitor TNBC response to NACT. This method utilises intravenously injected microbubbles, which consist of a gas core with an outer shell of lipid/albumin to image tumour microvasculature as well as gross tumour morphology. Trial Design: Single-centre study to evaluate HRCEUS to image the microvasculature of TNBC tumours in patients undergoing (NACT) and correlate imaging results with established markers of angiogenesis, proliferation and vasculogenic mimicry. Eligibility Criteria: Female, 18 to 60 years, histologically confirmed invasive TNBC with planned NACT, able to consent and in the Investigator’s opinion, adhering to the trial recommendations and governance. Aims: To investigate if imaging changes in the tumour microvasculature indicate a response to NACT and are reflected in the expression of proliferative markers. To determine whether changes in the tumour microvasculature and disease response are driven by angiogenesis +/- VM. To investigate whether overall disease response and changes in the microvasculature are influenced by the basal type phenotype or germline mutations in BRCA 1/2. Investigate patient satisfaction with the contrast ultrasound test. Statistical Methods: Quantify HRCEUS imaging characteristics of microvasculature at 3 treatment points. Compare this with the results of conventional imaging and the histopathological results of surgical excision at the end of NACT. Quantify immunohistochemical markers of angiogenesis, proliferation and VM at three treatment points and compare this with HRCEUS. Determine phenotype of all cases using immunohistochemistry to identify the basal Perform subtype analysis to assess if the basal phenotype is associated with imaging and immunohistochemical changes in the microvasculature during NACT. Test patients for germline BRCA1/2 gene mutations. Perform subtype analysis to assess if germline BRCA1/2 mutations are associated with imaging and immunohistochemical changes in the microvasculature during NACT. Present accrual (2 patients) and target accrual (5 patients) Contact details: j.rait@nhs.net Citation Format: Jaideep Rait, Michelle Garrett, Catherine Harper-Wynne, Sonia Saw, Mengxing Tang, Priya Palanisamy, Matthieu TOULEMONDE, Karina Cox. Imaging of tumour microvasculature using high-resolution contrast enhanced ultrasound together with markers of proliferation/angiogenesis/vascular mimicry to characterise response to NACT in TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-11.

Nogo-B modulates physiological and pathological angiogenesis during development and disease

Angiogenesis, i.e., the formation of new blood vessels, is essential for normal development and functional vessel formation in ischemic diseases. During angiogenesis, endothelial cells (ECs) coordinate migration, proliferation, and metabolic fluxes to adapt to branching vessels' increasing energy demands. Nogo-B is a ubiquitously expressed reticulon family protein mainly localized to the endoplasmic reticulum (ER) membrane. Our previous studies have shown that the genetic loss of Nogo-B results in aberrant vascular remodeling and dysregulated endothelial barrier function. The current study aims to examine the role of endothelial Nogo-B in regulating developmental angiogenesis and pathological angiogenesis in retinopathy of prematurity (ROP). We hypothesized that endothelial Nogo-B is required for physiological and pathological angiogenesis, and Nogo-B depletion attenuates pathological angiogenesis. Using tamoxifen-inducible, endothelial cell-specific Nogo-B−/− (Nogo-BiECKO) mice, Nogo-B global knockout mice, and C57Bl/6 (WT) mice, our results show that loss of Nogo-B in ECs significantly delayed Isolectin B4 (IB4)-labeled retinal blood vessel sprouting. Impaired EC proliferation was observed by the staining of and incorporation of 5-ethynyl-2′-deoxyuridine (EdU). Furthermore, using the Oxygen Induced Retinopathy (OIR) model to mimic ROP, we could demonstrate that loss of Nogo-B in EC resulted in reduced neovascularization compared to WT. Mechanistically, using Percoll gradients, ultra-resolution microscopy, proximity ligation assay, and electron-microscopy, we show that Nogo-B is localized in the mitochondria-associated ER membrane (MAM) and regulated MAM remodeling. Using seahorse assay, quantitative RT-PCR, and metabolomics analysis, we determined that loss of Nogo-B altered VEGF-mediated EC glycolysis, which is needed for the energy demand during angiogenesis. These data suggest that Nogo-B regulates glucose metabolism in EC and plays a pivotal role in physiological and pathological angiogenesis. Targeting endothelial Nogo-B may provide a plausible approach to controlling the formation of pathological neovascularization in retinal diseases, such as ROP, diabetic retinopathy, and wet forms of age-related macular degeneration. This work was supported by the National Institutes of Health (R01HL153599) and awards from the American Heart Association award to JY. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Advances in Engineered Nanoparticles for the Treatment of Ischemic Stroke by Enhancing Angiogenesis.

Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment.

Sevofluran Maruziyetinin Civciv Embriyo Gelişimi Üzerindeki Ex-Ovo Değerlendirilmesi: Anjiyogenez Etkilerinin Araştırılması

Objective: Angiogenesis, defined as the formation of new blood vessels from pre-existing ones, plays a vital role in both physiological and pathological conditions. Understanding agents that can influence angiogenesis is crucial in managing diseases where angiogenesis is dysregulated. This study focuses on sevoflurane, a commonly used inhalation anesthetic, whose effects on angiogenesis and embryonic development are not well understood. Our objective was to assess the impact of sevoflurane exposure on angiogenesis using the ex-ovo chick chorioallantoic membrane model. Methods: In this model, fertilized chicken eggs were exposed to sevoflurane at concentrations of 2% and 4%, for varying durations of 1, 2, and 4 hours. The embryos were then divided into control and experimental groups for quantitative angiogenesis assessment using Image J software, followed by statistical analysis with one-way analysis of variance. Results: The results indicate that sevoflurane exposure has a dose-dependent positive effect on angiogenesis, with significant increases in vascular density observed in embryos exposed to both concentrations compared to the control group. Additionally, the length of exposure was found to further enhance these angiogenic effects. Conclusion: Despite the dose and duration-dependent impact of sevoflurane on angiogenesis, the existing literature presents mixed findings, highlighting the need for additional research to elucidate sevoflurane’s role in angiogenesis. This is particularly important for understanding its implications in various medical conditions, such as cancer, wound healing, and fetal development. Future investigations into sevoflurane’s effects on placental angiogenesis could also provide valuable insights into its potential consequences on intrauterine growth. Keywords: Angiogenesis, sevoflurane, chicken embryo, model organisms, ex-ovo

EFFECT OF KECEMCEM (Spondias pinnata) EXTRACT ON ANGIOGENESIS OF GINGIVA AFTER CURETASE OF WISTAR RATS

Background: Curettage procedure cause wounds that require adjuvant therapy. One of adjuvant therapies used is hyaluronic acid. However, recently, several studies have focused on antioxidant and anti-inflammatory properties of various natural products such as the bark of kecemcem tree (Spondias pinnata) which has protective effect against oxidative and inflammatory changes occurs during development of mucositis. Based on this, researchers were interested examining effect of giving kecemcem bark extract on formation of new blood vessels (angiogenesis) in gingiva after curettage. Materials and Methods: Wistar rats were divided into 3 groups, negative control, positive control, and treatment group. Previously, rats had induced periodontal pockets by tying silk threads on mandibular incisors and after that they were curettage using a gracey curette. Negative control group was given CMC-Na, positive control group was given hyaluronic acid and treatment group was given 70% kecemcem bark extract gel. Rats were sacrificed on day 3, 5 and 7 and then histological preparations were made. Results and discussion: Average number of new blood vessels in the treatment group was higher than control group and positive control with two-way ANOVA test showed that average number of new blood vessels in each group had significant difference (p<0.05). This supports hypothesis that compounds found in the bark of the kecemcem tree such as beta-sitosterol, phenols, and flavonoids have effect on increasing angiogenesis in gingival wounds after curettage of Wistar rats. Conclusion: 70% kecemcem bark extract gel has effect on increasing angiogenesis in gingival wounds after curettage of Wistar rats.

Progress in the Use of Hydrogels for Antioxidant Delivery in Skin Wounds.

The skin is the largest organ of the body, and it acts as a protective barrier against external factors. Chronic wounds affect millions of people worldwide and are associated with significant morbidity and reduced quality of life. One of the main factors involved in delayed wound healing is oxidative injury, which is triggered by the overproduction of reactive oxygen species. Oxidative stress has been implicated in the pathogenesis of chronic wounds, where it is known to impair wound healing by causing damage to cellular components, delaying the inflammatory phase of healing, and inhibiting the formation of new blood vessels. Thereby, the treatment of chronic wounds requires a multidisciplinary approach that addresses the underlying causes of the wound, provides optimal wound care, and promotes wound healing. Among the promising approaches to taking care of chronic wounds, antioxidants are gaining interest since they offer multiple benefits related to skin health. Therefore, in this review, we will highlight the latest advances in the use of natural polymers with antioxidants to generate tissue regeneration microenvironments for skin wound healing.

Decoding Tumor Angiogenesis for Therapeutic Advancements: Mechanistic Insights.

Tumor angiogenesis, the formation of new blood vessels within the tumor microenvironment, is considered a hallmark of cancer progression and represents a crucial target for therapeutic intervention. The tumor microenvironment is characterized by a complex interplay between proangiogenic and antiangiogenic factors, regulating the vascularization necessary for tumor growth and metastasis. The study of angiogenesis involves a spectrum of techniques, spanning from biomarker assessment to advanced imaging modalities. This comprehensive review aims to provide insights into the molecular intricacies, regulatory dynamics, and clinical implications of tumor angiogenesis. By delving into these aspects, we gain a deeper understanding of the processes driving vascularization in tumors, paving the way for the development of novel and effective antiangiogenic therapies in the fight against cancer.

Eriocitrin Inhibits Angiogenesis by Targeting VEGFR2-Mediated PI3K/AKT/mTOR Signaling Pathways.

Eriocitrin, a flavanone found in peppermint and citrus fruits, is known to possess many physiological activities. However, the anti-angiogenic effects of eriocitrin are yet to be fully elucidated. Therefore, the objective of this research was to explore the anti-angiogenic effects of eriocitrin both in vitro and in vivo as well as its underlying mechanism. Anti-angiogenic effects of eriocitrin were evaluated utilizing in vitro models of angiogenesis, including inhibition of tube formation, and induction of apoptosis in human umbilical vein endothelial cells (HUVECs). A chorioallantoic membrane (CAM) assay in chick embryos was also performed to evaluate the in vivo effects of eriocitrin on angiogenesis. Results showed significant eriocitrin effects on proliferation, tube formation, migration, and apoptosis in HUVECs. Furthermore, in vivo analysis revealed that eriocitrin significantly suppressed the formation of new blood vessels. In particular, it regulated MAPK/ERK signaling pathway and VEGFR2, inhibited the downstream PI3K/AKT/mTOR signaling pathway, and activated apoptosis signals such as caspase cascades. In HUVECs, the expression of matrix metalloproteinases (MMP-2 and MMP-9) exhibited an inhibitory effect on angiogenesis through the suppression of the signaling pathway. Therefore, eriocitrin presents potential for development into an antiangiogenic therapeutic agent.

Prostanoids Regulate Angiogenesis and Lymphangiogenesis in Pathological Conditions.

Angiogenesis, the formation of new blood vessels from the preexistent microvasculature, is an essential component of wound repair and tumor growth. Nonsteroidal anti-inflammatory drugs that suppress prostanoid biosynthesis are known to suppress the incidence and progression of malignancies including colorectal cancers, and also to delay the wound healing. However, the precise mechanisms are not fully elucidated. Accumulated results obtained from prostanoid receptor knockout mice indicate that a prostaglandin E-type receptor signaling EP3 in the host microenvironment is critical in tumor angiogenesis inducing vascular endothelial growth factor A (VEGF-A). Further, lymphangiogenesis was also enhanced by EP signaling via VEGF-C/D inductions in pathological settings. These indicate the importance of EP receptor to facilitate angiogenesis and lymphangiogenesis in vivo. Prostanoids act beyond their commonly understood activities in smooth muscle contraction and vasoactivity, both of which are quick responses elicited within several seconds on stimulations. Prostanoid receptor signaling will be a potential therapeutic target for disease conditions related to angiogenesis and lymphangiogenesis.

Experimental study of Pruthvisara taila in excised wound model in Wistar albino rats

Pruthvisara taila is a formulation indicated in the chikitsa of vrana as topical medicine in classical text Chakradatta. It contains Shuddha chitrakamoola, Shuddha vatsanabha, Shuddha karaveera, Nirgundi moola, Nadibeeja, Kanji and Karanja taila as the base. Aims and Objectives: Evaluation of wound healing property of Pruthvisara taila through experimental study. Methodology: Wound healing property in albino rats by excision wound healing model and its histopathology study. Results: Results of the study on the parameters assessed like percentage of wound contraction and histopathology study; percentage of wound closure was observed in Control group was 94.92%, in standard it was 93.73% and in test drug the percentage of wound contraction was 95.73%.The test drug, Pruthvisara taila showed more angiogenesis and formation of new blood vessels than standard group and in control group there was absence of formation of new blood vessels and proliferation of fibroblast cells. The control group did not show any collagen formation and scab formation the test drug Pruthvisara taila showed moderate formation and deposition compared to standard drug. Compared to control and standard group, the test drug, Pruthvisara taila selected in this study showed remarkable wound healing property in excised wound.

Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights.

Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous vegetables, has garnered attention for its anticancer properties. This review synthesizes existing research on PEITC, focusing on its mechanisms of action in combatting cancer. PEITC has been found to be effective against various cancer types, such as breast, prostate, lung, colon, and pancreatic cancers. Its anticancer activities are mediated through several mechanisms, including the induction of apoptosis (programmed cell death), inhibition of cell proliferation, suppression of angiogenesis (formation of new blood vessels that feed tumors), and reduction of metastasis (spread of cancer cells to new areas). PEITC targets crucial cellular signaling pathways involved in cancer progression, notably the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Protein Kinase B (Akt), and Mitogen-Activated Protein Kinase (MAPK) pathways. These findings suggest PEITC's potential as a therapeutic agent against cancer. However, further research is necessary to determine the optimal dosage, understand its bioavailability, and assess potential side effects. This will be crucial for developing PEITC-based treatments that are both effective and safe for clinical use in cancer therapy.

Enhancing bone tissue engineering using iron nanoparticles and magnetic fields: A focus on cytomechanics and angiogenesis in the chicken egg chorioallantoic membrane model.

To evaluate the potential of iron nanoparticles (FeNPs) in conjunction with magnetic fields (MFs) to enhance osteoblast cytomechanics, promote cell homing, bone development activity, and antibacterial capabilities, and to assess their in vivo angiogenic viability using the chicken egg chorioallantoic membrane (CAM) model. Experimental study conducted in a laboratory setting to investigate the effects of FeNPs and MFs on osteoblast cells and angiogenesis using a custom titanium (Ti) substrate coated with FeNPs. A custom titanium (Ti) was coated with FeNPs. Evaluations were conducted to analyze the antibacterial properties, cell adhesion, durability, physical characteristics, and nanoparticle absorption associated with FeNPs. Cell physical characteristics were assessed using protein markers, and microscopy, CAM model, was used to quantify blood vessel formation and morphology to assess the FeNP-coated Ti's angiogenic potential. This in vivo study provided critical insights into tissue response and regenerative properties for biomedical applications. Statistical analysis was performed using appropriate tests to compare experimental groups and controls. Significance was determined at P < 0.05. FeNPs and MFs notably improved osteoblast cell mechanical properties facilitated the growth and formation of new blood vessels and bone tissue and promoted cell migration to targeted sites. In the group treated with FeNPs and exposed to MFs, there was a significant increase in vessel percentage area (76.03%) compared to control groups (58.11%), along with enhanced mineralization and robust antibacterial effects (P < 0.05). The study highlights the promising potential of FeNPs in fostering the growth of new blood vessels, promoting the formation of bone tissue, and facilitating targeted cell migration. These findings underscore the importance of further investigating the mechanical traits of FeNPs, as they could significantly advance the development of effective bone tissue engineering techniques, ultimately enhancing clinical outcomes in the field.

Vascular Endothelial Growth Factor Expression by Immunohistochemistry as a Possible Indicator of Prognosis in Invasive Breast Carcinoma of No Special Type

Context: Angiogenesis, the formation of new blood vessels from preexisting vascular network, is essential for tumor growth and spread. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor. Aims: To assess the expression of VEGF in invasive carcinoma of no special type and its correlation with all the known prognostic factors of breast carcinoma. Settings and Design: Descriptive. Materials and Methods: Mastectomy specimens were studied noting the clinical details. The formalin-fixed tissues were subjected to routine processing and hematoxylin and eosin sections and studied extensively for all the histological prognostic factors. Representative sections from each case with the tumor were subjected to immunohistochemistry (IHC) staining with VEGF, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) antibodies. Statistical Analysis Used: Descriptive statistics, Chi-square tests, contingency table analysis using SPSS for Windows. Results: One hundred and twelve cases of invasive carcinoma of special type were studied to evaluate various clinicopathological parameters. The association of VEGF with clinicopathological parameters and all the known prognostic factors was studied to note its significance. VEGF overexpression was observed in 69% of the cases. It was noted that larger tumor size, higher histological grade, lymphovascular invasion, nodal involvement, tumor necrosis, high microvessel density, ER negativity, PR negativity, and HER2/neu positivity had a significant statistical association with VEGF overexpression. Conclusions: We conclude that incorporating VEGF as a biomarker along with the known factors into a prognostic index will not only help predict clinical outcome more accurately, but also determines the patient who can be benefited with combinational therapy including anti-VEGF factors.

Flavonoids with Anti-Angiogenesis Function in Cancer.

The formation of new blood vessels, known as angiogenesis, significantly impacts the development of multiple types of cancer. Consequently, researchers have focused on targeting this process to prevent and treat numerous disorders. However, most existing anti-angiogenic treatments rely on synthetic compounds and humanized monoclonal antibodies, often expensive or toxic, restricting patient access to these therapies. Hence, the pursuit of discovering new, affordable, less toxic, and efficient anti-angiogenic compounds is imperative. Numerous studies propose that natural plant-derived products exhibit these sought-after characteristics. The objective of this review is to delve into the anti-angiogenic properties exhibited by naturally derived flavonoids from plants, along with their underlying molecular mechanisms of action. Additionally, we summarize the structure, classification, and the relationship between flavonoids with their signaling pathways in plants as anti-angiogenic agents, including main HIF-1α/VEGF/VEGFR2/PI3K/AKT, Wnt/β-catenin, JNK1/STAT3, and MAPK/AP-1 pathways. Nonetheless, further research and innovative approaches are required to enhance their bioavailability for clinical application.

Alternating Current-Electric Field Inducing Chorio Allantoic Membrane (CAM) Angiogenesis through Exogenous Growth Factor Intervention

Angiogenesis is widely used in various therapies by promoting or inhibiting the formation of new blood vessels. The use of Alternating Current-Electric Fields (AC-EF) in Electro-Capacitive Cancer Therapy (ECCT) showed its potential as an anti-cancer device, and is characterized by its anti-proliferative and pro-apoptotic effects. However, the role of AC-EF in angiogenesis remains unclear. To investigate the effects of AC-EF on CAM angiogenesis, we used the ex ovo culture method of chorioallantoic membrane (CAM). A basic fibroblast growth factor (bFGF) dose of 30 ng/µL was administered as an exogenous growth factor. The ECCT device, generating AC-EF of 150 kHz and 18 Vpp, was exposed to the CAMs. Subsequently, the 24 CAMs of chick embryo were divided into four groups. Two groups were non-bFGF-induced CAM, while the other two were bFGF-induced CAM, and each group was exposed either with or without AC-EF. The vascularization was evaluated through macroscopic observation, while vascular endothelial growth factor A (VEGFA) gene expression was measured using qPCR. The data were statistically analyzed using ANOVA with GraphPad Prism 9.5. The results showed that an AC-EF exposure had no effects on normal CAM angiogenesis (P&gt;0.05). Moreover, VEGFA gene expression did not show significant upregulation (P&gt;0.05) in the bFGF-induced CAM with or without AC-EF exposure. Interestingly, the number of new blood vessels was significantly higher (P&lt;0.05) in the bFGF-induced with AC-EF exposure than in the non-bFGF-induced group. In conclusion, AC-EF of ECCT did not affect normal angiogenesis. AC-EF may trigger CAM angiogenesis with bFGF induction. This observation suggested that AC-EF of intermediate frequency could enhance angiogenesis by administration of external growth factors, offering a potential avenue for addressing obstructive vascular conditions.

A nano-composite hyaluronic acid-based hydrogel efficiently antibacterial and scavenges ROS for promoting infected diabetic wound healing

Diabetic wound infection brings chronic pain to patients and the therapy remains a crucial challenge owing to the disruption of the internal microenvironment. Herein, we report a nano-composite hydrogel (ZnO@HN) based on ZnO nanoparticles and a photo-trigging hyaluronic acid which is modified by o-nitrobenzene (NB), to accelerate infected diabetic wound healing. The diameter of the prepared ZnO nanoparticle is about 50 nm. X-ray photoelectron spectroscopy (XPS) analysis reveals that the coordinate bond binds ZnO in the hydrogel, rather than simple physical restraint. ZnO@HN possesses efficient antioxidant capacity and it can scavenge DPPH about 40 % in 2 h and inhibit H2O2 >50 % in 8 h. The nano-composite hydrogel also exhibits satisfactory antibacterial capacity (58.35 % against E. coli and 64.03 % against S. aureus for 6 h). In vitro tests suggest that ZnO@HN is biocompatible and promotes cell proliferation. In vivo experiments reveal that the hydrogel can accelerate the formation of new blood vessels and hair follicles. Histological analysis exhibits decreased macrophages, increased myofibroblasts, downregulated TNF-α expression, and enhanced VEGFA expression during wound healing. In conclusion, ZnO@HN could be a promising candidate for treating intractable infected diabetic skin defection.

Deoxynivalenol Damages Corneal Epithelial Cells and Exacerbates Inflammatory Response in Fungal Keratitis.

Fungal keratitis (FK) is a kind of infectious keratopathy with a high rate of blindness worldwide. Deoxynivalenol (DON) has been proven to have multiple toxic effects on humans and animals. The aim of this study was to explore a possible pathogenic role of DON in FK. We first made an animal model of FK in New Zealand white rabbits, and then attempted to detect DON in a culture medium in which Fusarium solani had been grown and also in the corneal tissue of the animal model of Fusarium solani keratitis. Next, a model of DON damage in human corneal epithelial cells (HCECs) was constructed to evaluate effects of DON on the activity, migration ability, cell cycle, and apoptosis in the HCECs. Then, putative the toxic damaging effects of DON on rabbit corneal epithelial cells and the impact of the repair cycle were studied. The expression levels of inflammatory factors in the corneas of the animal model and in the model of DON-damaged HCECs were measured. The Fusarium solani strain used in this study appeared to have the potential to produce DON, since DON was detected in the corneal tissue of rabbits which had been inoculated with this Fusarium solani strain. DON was found to alter the morphology of HCECs, to reduce the activity and to inhibit the proliferation and migration of HCECs. DON also induced the apoptosis and S-phase arrest of HCECs. In addition, DON was found to damage rabbit corneal epithelial cells, to prolong the corneal epithelial regeneration cycle, and to be associated with the upregulated expression of inflammatory factors in HCECs and rabbit corneas. DON appears to have a toxic damaging effect on HCECs in FK, and to induce the expression of inflammatory factors, leading to the exacerbation of keratitis and the formation of new blood vessels. Future studies will explore the possibility of developing a test to detect DON in ophthalmic settings to aid the rapid diagnosis of FK, and to develop DON neutralizers and adsorbents which have the potential to improve keratocyte status, inhibit apoptosis, and alleviate inflammation, therein providing new thinking for therapy of clinical FK.