Search Results (770)

Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L. var. sylvestris (Lam.) Fiori), the wild cardoon, is known for its culinary applications and potential health benefits. Due to this, and given the growing interest in circular economies, deepening our under-standing of the effects of wild cardoon leaf waste on angiogenesis and collagenase activity represents a valuable opportunity to valorise agricultural byproducts as health-promoting ingredients. In this study, the waste product of wild cardoon leaves was extracted to examine its chemical composition and biological activities. Analytical techniques identified several bioactive compounds, including flavonoids, hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids, and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos and the chick chorioallantoic membrane demonstrated dose-dependent antiangiogenic effects, particularly enhanced by the complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD). Considering the link between angiogenesis and collagenase, the potential effects of the extract on collagenase activity was investigated. The extract alone inhibited collagenase with an IC₅₀ value comparable to that of the standard inhibitor while its complexed form exhibited a 4.5-fold greater inhibitory activity. A molecular docking study examined the interaction between the main compounds and collagenase. In conclusion, wild cardoon leaves can represent a valuable source of bioactive compounds. This study demonstrated that the complexation of the extract with cyclodextrin determines an increase in its biological activity. Full article

The application of artificial intelligence through the brain–computer interface (BCI) is proving to be one of the great advances in neuroscience today. The development of surface electrodes over the cortex and very fine electrodes that can be stereotactically implanted in the brain have moved the science forward to the extent that paralyzed people can play chess and blind people can read letters. However, the introduction of foreign bodies into deeper parts of the central nervous system results in foreign body reaction, scarring, apoptosis, and decreased signaling. Implanted electrodes activate microglia, causing the release of inflammatory factors, the recruitment of systemic inflammatory cells to the site of injury, and ultimately glial scarring and the encapsulation of the electrode. Recordings historically fail between 6 months and 1 year; the longest BCI in use has been 7 years. This article proposes a biomolecular strategy provided by angiogenic cell precursors (ACPs) and nerve cell precursors (NCPs), administered intrathecally. This combination of cells is anticipated to sustain and promote learning across the BCI. Together, through the downstream activation of neurotrophic factors, they may exert a salutary immunomodulatory suppression of inflammation, anti-apoptosis, homeostasis, angiogenesis, differentiation, synaptogenesis, neuritogenesis, and learning-associated plasticity. Full article

This review highlights recent findings on the potent anti-angiogenic serpin protein, pigment epithelium-derived factor (PEDF) as it relates to metabolic disease, diabetes, angiogenesis and cardiovascular disease (CVD), listing a majority of all the publicly available studies reported to date. PEDF is involved in various physiological roles in the body, and when awry, it triggers various disease states clinically. Biomarkers such as insulin, AMP-activated protein kinase alpha (AMPK-α), and peroxisome proliferator-activated receptor gamma (PPAR-γ) are involved in PEDF effects on metabolism. Wnt, insulin receptor substate (IRS), Akt, extracellular signal-regulated kinase (ERK), and mitogen-activated protein kinase (MAPK) are implicated in diabetes effects displayed by PEDF. For CVD, oxidised LDL, Wnt/β-catenin, and reactive oxygen species (ROS) are players intertwined with PEDF activity. The review also presents an outlook on where efforts could be devoted to bring this serpin closer to clinical trials for these diseases and others in general. Full article

Cancer is a serious group of diseases that is a huge problem on a global scale and is the second most common cause of death. Commonly used therapies do not always lead to the complete elimination of diseased cells or tissues and are also burdened with side effects that reduce the quality of life of patients. Due to these difficulties, new therapeutic approaches are still being sought. In recent years, there has been a return to interest in natural methods of treating various diseases, among which phytochemicals are particularly interesting. This article reviews plant extracts with anticancer properties with different mechanisms of action (proapoptotic, antiproliferative, antiangiogenic, immunomodulatory). In addition, plant extracts that reduce the side effects of chemotherapy and the limitations and prospects for the use of plant extracts in anticancer therapy are described. Our goal was to create an up-to-date information base that would encourage scientists to intensify research into supplementing targeted anticancer therapies with additional protective and preventive measures, in which natural mixtures of phytochemicals (plant extracts) are effective allies. At the same time, we encourage discussion on the limitations of their use in light of the orthodox principles of classical medicine and pharmacy (issues of safety, quality, drug purity, and dose precision), which are a priori correct but have not yet led to the elimination of cancer from the group of incurable diseases. Full article

Stem cells cultured in cell aggregates exhibit higher cell survival rates and enhanced anti-inflammatory and angiogenic effects compared to single cells, constructing a stable and economical cell aggregate culture system that can accurately adjust the mass transfer distance of nutrients, which contributes to improving the therapeutic effects of stem cell aggregates. In this study, an alginate hydrogel microsphere culture system (Alg-HM) was prepared using electrostatic spraying technology and refined by optimizing the electrostatic spraying technology parameters, such as the sodium alginate concentration, voltage, electrospray injection speed, and nozzle inner diameter. Furthermore, by setting the Tip-dropped culture system (Tip-D culture system, created by dropping the resuspended hMSC aggregate–hydrogel solution with a tip to form the hydrogel microsphere) and Matrigel culture system (created by dropping the resuspended hMSC aggregates–Matrigel solution with a tip to form the Matrigel culture system) as the control group and Alg-HM as the experimental group, the culture effect of hMSC aggregates in the optimized Alg-HM culture system was tested; CCK-8 detection and Ki-67 immunofluorescence staining showed that the Alg-HM culture system significantly enhanced the cell proliferation activity of hMSC aggregates after 7 and 14 days of culture. The Calcein-AM/PI cell staining results showed that the Alg-HM culture system can significantly reduce the central necrosis of hMSC aggregates. The RNA sequencing results showed that the Alg-HM culture system can significantly activate the signaling pathways related to cell proliferation in hMSCs. This culture system is helpful for the culture of cell aggregates in vitro and efficient transplantation in vivo. Full article

Background/Objectives: Tetrastatin, the globular non collagenous (NC1) domain of the α4 chain of collagen IV, was previously demonstrated to inhibit melanoma progression. We identified the minimal active sequence (QKISRCQVCVKYS: QS-13) that reproduced the anti-tumor effects of whole Tetrastatin and demonstrated its anti-angiogenic activity mediated through αvβ3 and α5β1 binding. As QS-13 peptide was not fully soluble in aqueous solution, we designed new peptides with better water solubility. The present work aimed to investigate the interactions of ten QS-13-derived peptides, exhibiting improved hydro-solubility, with αvβ3 and α5β1 integrins. Methods: Using bioinformatics tools such as GROMACS, VMD, and the Autodock4 suite, we investigated the ability of the substituted peptides to bind αvβ3 and α5β1 integrins in silico. Results: We demonstrated in silico that all substituted peptides were able to bind both integrins at the RGD-binding site and determined their theoretical binding energy. Conclusions: The new soluble peptides should be able to compete with natural integrin ligands such as fibronectin, but also FGF1, FGF2, IGF1, and IGF2. Taken together, these findings suggest that the QS-13-derived peptides are reliable anti-angiogenic and anti-tumor agents. Full article

Systemic cancer progression culminating in metastatic disease is implicitly dependent on tumour cell interactions with the vascular system. Indeed, different facets of the micro- and macro-vasculature can be regarded as rate-limiting ‘vascular checkpoints’ in the process of cancer dissemination. The underlying complex communication networks drive tumour neovascularization, angiogenesis, immunoregulation, activation of the coagulation system, angiocrine interactions, and non-angiogenic vascular responses across multiple cancer types. Yet, each cancer may represent a unique vascular interaction scenario raising a prospect of targeted modulation of blood and lymphatic vessels for therapeutic purposes, beyond the traditional notion of tumour anti-angiogenesis. While the emphasis of studies aiming to understand this circuitry has traditionally been on soluble, or ‘mono-molecular’ mediators, the rise of the particulate secretome encompassing heterogeneous subpopulations of extracellular vesicles (EVs; including exosomes) and particles (EPs) brings another dimension into the tumour–vascular communication web during the process of metastasis. EVs and EPs are nanosized cellular fragments, the unique nature of which lies in their ability to encapsulate, protect and deliver to target cells a range of bioactive molecular entities (proteins, RNA, DNA) assembled in ways that enable them to exert a wide spectrum of biological activities. EVs and EPs penetrate through biological barriers and are capable of intracellular uptake. Their emerging vascular functions in metastatic or infiltrative cancers are exemplified by their roles in pre-metastatic niche formation, thrombosis, vasectasia or angiocrine regulation of cancer stem cells. Here, we survey some of the related evidence supporting the biological, diagnostic and interventional significance of EVs/EPs (EVPs) in disseminated neoplastic disease. Full article

Atrial fibrillation (AF), the most prevalent clinically significant cardiac arrhythmia, is characterized by chaotic atrial electrical activity and currently affects an estimated 2.5–3.5% of the global population. Its pathogenesis involves ion channel dysfunction, inflammatory cascades, and structural remodeling processes, notably fibrosis. Angiogenesis, the physiological/pathological process of new blood vessel formation, plays a multifaceted role in AF progression. This review synthesizes evidence highlighting angiogenesis’s dual role in AF pathogenesis: while excessive or dysregulated angiogenesis promotes atrial remodeling through fibrosis, and electrical dysfunction via VEGF, ANGPT, and FGF signaling pathways, compensatory angiogenesis exerts protective effects by improving tissue perfusion to alleviate ischemia and inflammation. Therapeutically, targeting angiogenic pathways—particularly VEGF—represents a promising strategy for modulating structural remodeling; however, non-selective VEGF inhibition raises safety concerns due to cardiovascular toxicity, necessitating cautious exploration. Emerging evidence highlights that anti-cancer agents (e.g., ibrutinib, bevacizumab) impair endothelial homeostasis and elevate AF risk, underscoring the need for cardio-oncology frameworks to optimize risk–benefit ratios. Preclinical studies on angiogenesis inhibitors and gene therapies provide mechanistic insights, but clinical validation remains limited. Future research should prioritize elucidating mechanistic complexities, developing biomarker refinement, and implementing interdisciplinary strategies integrating single-cell sequencing with cardio-oncology principles. This review emphasizes the imperative to clarify angiogenic mechanisms, optimize therapeutic strategies, and balance pro-arrhythmic versus compensatory angiogenesis, in pursuit of personalized AF management. Full article

Background/Objectives: Nucleic acid-based anticancer vaccines are becoming a very active field in the fight against cancer. Here, our goal was to generate an oral DNA vaccine targeting the angiogenic peptide, proadrenomedullin N-terminal 20 peptide (PAMP). Methods: An expression plasmid (PcPAMP) was generated by fusing the tetanus toxin epitopes P2 and P30 to the mouse PAMP sequence to counteract self-tolerance, and the empty plasmid was used as a negative control (PcNeg). The plasmids were introduced into Salmonella typhimurium bacteria that were then transformed into bacterial ghosts. C57BL/6J mice were orally immunized with the ghosts five times at 2-week intervals. Then, B16-F10 melanoma cells were injected into the tail vein to generate lung metastases. Furthermore, naïve CD4⁺ T cells were exposed to PAMP, and their secretome was analyzed by proximity extension assays. Results: Significant levels of anti-PAMP immunoglobulins were detected in the blood of PcPAMP-vaccinated mice and their levels of spleen CD8⁺ T cells were significantly higher than in those treated with PcNeg, indicating that self-tolerance was effectively broken. Although the number and size of lung metastases was similar between both experimental groups, there was a significant reduction in intratumoral angiogenesis and in cancer cell proliferation index in the PcPAMP group. Furthermore, these animals showed an intense infiltration of lymphocytes, including regulatory T cells, and M2-like macrophages into the metastases, that was not evident in the PcNeg group. In addition, PAMP induced upregulation of IL1β, IL6, IL7, IL12, IL27, TNFα, and FGF21, and downregulation of IL16 in naïve CD4⁺ T cells. Conclusions: Although the vaccine was not effective in reducing tumor growth, new proliferative and immune functions have been described for PAMP. These new functions include induction of melanoma proliferation and modulation of lymphocyte and macrophage tumor infiltration dynamics. Full article

A comparative evaluation of Moringa oleifera Lam. ethanolic leaf extracts was performed using different extraction methods (maceration or ultrasound-assisted) and the qualitative and quantitative profile of the bioactive compounds contained were further assessed. The antioxidant potential and antimicrobial activity were evaluated, as well as the antiangiogenic effects through in ovo studies. Six ethanolic extracts were tested in this study. Moringa MAC 70% and Moringa US 70% extracts displayed the highest concentration of phenolic compounds and also showed a significant AOA at the highest tested dose. Regarding the antimicrobial effect, the extracts obtained with 70% ethanol (maceration or ultrasound-assisted) had antimicrobial activity against S. aureus, S. pyogenes and E. coli, followed by Candida parapsilosis. On the Pseudomonas aeruginosa strain, the extracts showed no effect. The HET-CAM assay showed that the extracts did not cause any irritation compared to the used positive control. Furthermore, the extracts Moringa MAC 70% and Moringa US 70% did not affect the normal process of blood vessel formation. The data obtained highlights that, from the six tested extracts, the ones obtained with 70% ethanol using maceration and ultrasound-assisted methods (Moringa MAC 70% and Moringa US 70%) showed the highest phenolic content and exhibited the strongest antioxidant activity. The same two extracts did not show signs of irritation in the HET-CAM model. Full article

Glioblastoma, classified as a grade IV astrocytoma, is an aggressive and malignant primary brain tumor with no known cure. Despite the implementation of standard medical and surgical treatment protocols, the disease often progresses with unsatisfactory outcomes. This study aimed to evaluate the cytotoxic, proapoptotic, and antimetastatic effects of anti-angiogenic monoclonal antibody bevacizumab combined with the sphingosine-1-phosphate receptor modulator fingolimod on rat glioma C6 cells. The cytotoxicity of bevacizumab and fingolimod was evaluated using the MTT assay. Proapoptotic activity was assessed through flow cytometric analyses, including Annexin V–FITC staining, caspase 3/7 activation, and mitochondrial membrane potential measurements. Morphological changes were examined using confocal microscopy. Antimetastatic effects were evaluated via anti-migration and colony formation assays. The combination of bevacizumab and fingolimod exhibited antiproliferative, cytotoxic, proapoptotic, and antimetastatic effects on C6 glioma cells at low IC₅₀ concentrations. Based on growth inhibitory, proapoptotic, and antimetastatic activities on C6 glioma cells, the combination of bevacizumab and fingolimod demonstrates significant growth-inhibitory, proapoptotic, and antimetastatic activities against C6 glioma cells, suggesting its potential as a promising pharmacotherapeutic approach for the treatment of glioblastoma. Full article

Background/Objectives: This study evaluated the potential of a polysaccharide (PCS) extracted from the brown alga Cystoseira spinosa as an antioxidant and anti-inflammatory agent. Collected off the coast of Alkhoms, Libya, PCS was investigated for its wound-healing and pro-angiogenic properties, addressing the need for natural bioactive compounds in therapeutic applications. Methods: The monosaccharide composition of PCS was analyzed using HPLC-RID, identifying glucuronic acid and xylose as major components. In vitro tests assessed antioxidant activity, while in vivo experiments on 24 rats evaluated wound healing. Rats were divided into four groups: control (saline), standard drug (CYTOL CENTELLA cream), glycerol, and glycerol+PCS. Wound healing was analyzed macroscopically, histologically, and biochemically. The chick chorioallantoic membrane (CAM) model assessed pro-angiogenic effects, and computational analyses explored COX-2 and VEGF pathways. Pharmacokinetic properties were also evaluated. Results: PCS demonstrated significant antioxidant activity and accelerated wound healing after 16 days, with improved wound appearance scores and increased collagen content. Histological analysis confirmed PCS outperformed the standard drug. The CAM model showed PCS increased blood vessel density, length, and junctions while reducing lacunarity. Computational analyses supported involvement of COX-2 and VEGF pathways. Pharmacokinetic assessments indicated good bioavailability, non-inhibition of CYP enzymes, and favorable skin permeability. Conclusions: PCS shows promise as a natural bioactive polymer for wound healing and tissue regeneration. Its antioxidant, anti-inflammatory, and pro-angiogenic properties, combined with favorable pharmacokinetics, highlight its therapeutic potential. This study provides new insights into the mechanisms of C. spinosa polysaccharides and their application in promoting tissue repair. Full article

Tumor angiogenesis and metastasis are critical processes in the progression of colon carcinoma. Curcumol, a bioactive sesquiterpenoid derived from curcuma, exhibits anti-angiogenic properties, though its underlying mechanisms remain unclear. In this study, an HT-29 xenograft mouse model demonstrated that curcumol combined with oxaliplatin significantly suppressed tumor growth (Ki67↓) and microvessel density (CD31↓). In vitro assays revealed that curcumol dose dependently inhibited proliferation (MTT), migration (Transwell), and tube formation (CAM assay) in Caco-2/HT-29 and HUVEC cells. Mechanistically, curcumol downregulated OTUB1 expression, promoting TGFB1 degradation via the ubiquitin–proteasome pathway. OTUB1 overexpression activated the TGFB1/VEGF axis, enhancing cell invasiveness and angiogenesis—effects reversed by high-dose curcumol. These findings identify the OTUB1-TGFB1/VEGF axis as a key target of curcumol in inhibiting colon cancer angiogenesis, elucidating its anti-tumor mechanism and offering a novel therapeutic strategy for targeted treatment. Full article

Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine when bladder pressure exceeds urethral closing pressure during routine activities such as physical exertion, coughing, exercise, or sneezing. SUI is the most prevalent form of urinary incontinence, with a reported prevalence ranging from 10% to 70%, and its incidence increases with age. As the global population continues to age, the prevalence and clinical significance of SUI are expected to rise accordingly. The pathophysiology of SUI is primarily driven by two mechanisms: urethral hypermobility, resulting from compromised supporting structures, and intrinsic urethral sphincter deficiency, characterized by the deterioration of urethral mucosa and muscle tone. Current treatment options for SUI include conservative management strategies, which heavily rely on patient adherence and are associated with high recurrence rates, and surgical interventions, such as sling procedures, which offer effective solutions but are costly and carry the risk of adverse side effects. These limitations highlight the urgent need for more effective and comprehensive treatment modalities. Exosomes, nano-sized (30–150 nm) extracellular vesicles secreted by nearly all cell types, have emerged as a novel therapeutic option due to their regenerative, anti-fibrotic, pro-angiogenic, anti-apoptotic, anti-inflammatory, and anti-hypoxic properties. These biological functions position exosomes as a promising alternative to conventional therapies for SUI. Exosome therapy has the potential to enhance tissue regeneration, restore urethral function, and repair nerve and muscle damage, thereby reducing symptom burden and improving patients’ quality of life. Additionally, exosome-based treatments could offer a less invasive alternative to surgery, potentially decreasing the need for repeated interventions and minimizing complications associated with current procedures. In this literature review, we critically assess the current state of research on the potential use of exosomes in treating SUI, highlighting their therapeutic mechanisms and potential clinical benefits. Full article

Angiogenesis plays a crucial role in solid tumor growth. Ischemia and inflammation induce various angiogenic mediators, and patient metabolic conditions importantly influence this process. Macrophages closely interact with the vascular system and regulate angiogenesis through pro/anti-angiogenic factors. Traditionally, pro-angiogenic activity has been attributed to M2-like macrophages. We question this, as recent evidence suggests that also M1-like macrophages can be pro-angiogenic. Therefore, the aim is to identify the pro/anti-angiogenic gene expression profiles of human polarized macrophages unbiasedly. We also examine the effect of hyperglycemia on angiogenic gene expression, reflecting its role in diabetes and other metabolic conditions. Bioinformatic analysis was performed on the angiogenesis-related gene expression profiles of CD14+ monocyte-derived M1(IFN-γ)- and M2(IL-4)-polarized macrophages. The top differentially expressed genes were selected for validation. Macrophages were generated in vitro and polarized to M1(IFN-γ) and M2(IL-4/IL-6) cells under standard/hyperglycemic conditions. After immunophenotypic confirmation, selected gene expression was quantified using qPCR. IL-4 and IL-6 induce distinct M2-like phenotypes with mixed pro/anti-angiogenic gene expression. Remarkably, IFN-γ stimulation also increases several pro-angiogenic genes. Hyperglycemia affects the angiogenic expression profile in both M1- and M2-like macrophages, although distinctive identities remain intact. The pro-angiogenic phenotype is not limited to M2-polarized macrophages. Both M1- and M2-like macrophages express complex pro/anti-angiogenic gene profiles, which are only mildly influenced by hyperglycemia. Full article