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Angiogenesis is a crucial process for tissue development, repair, and tumor survival. Vascular endothelial growth factor (VEGF) is a key driver secreted by cancer cells, promoting neovascularization. While VEGF's role in angiogenesis is well-documented, its influence on the other aspects in tumor microenvironemt is less discussed. This review elaborates on VEGF's impact on intercellular interactions within the tumor microenvironment, including how VEGF affects pericyte proliferation and migration and mediates interactions between tumor-associated macrophages and cancer cells, resulting in PDL-1-mediated immunosuppression and Nrf2-mediated epithelial-mesenchymal transition. The review discusses VEGF's involvement in intra-organelle crosstalk, tumor metabolism, stemness, and epithelial-mesenchymal transition. It also provides insights into current anti-VEGF therapies and their limitations in cancer treatment. Overall, this review aims to provide a thorough overview of the current state of knowledge concerning VEGF signaling and its impact, not only on angiogenesis but also on various other oncogenic processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or personal interests that could have appeared to influence the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The vascular endothelial growth factor (VEGF) family of cytokines plays a key role in vasculogenesis, angiogenesis, and lymphangiogenesis. VEGF-A is the main member of this family, alongside placental growth factor (PlGF), VEGF-B/C/D in mammals, and VEGF-E/F in other organisms. To study the activities of these growth factors under physiological and pathological conditions, resulting in therapeutic applications in cancer and age-related macular degeneration, blocking ligands have been developed. These have mostly been large biomolecules like antibodies. Ligands with high affinities, at least in the nanomolar range, and accurate structural data from X-ray crystallography and NMR spectroscopy have been described. They constitute the main focus of this overview, which evidences similarities and differences in their binding modes. For VEGF-A ligands, and to a limited extent also for PlGF, a transition is now observed towards developing smaller ligands like nanobodies and peptides. These include unnatural amino acids and chemical modifications for designed and improved properties, such as serum stability and greater affinity. However, this review also highlights the scarcity of such small molecular entities and the striking lack of small organic molecule ligands. It also shows the gap between the rather large array of ligands targeting VEGF-A and the general absence of ligands binding other VEGF members, besides some antibodies. Future developments in these directions are expected in the upcoming years, and the study of these growth factors and their promising therapeutic applications will be welcomed.

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, a physiological process characterized by the formation of new vessels from a preexisting endothelium. VEGF has also been implicated in pathologic states, such as neoplasias, intraocular neovascular disorders, among other conditions. VEGFs are distributed in seven different families: VEGF-A, B, C, D, and PIGF (placental growth factor), which are identified in mammals; VEGF-E, which are encountered in viruses; and VEGF-F or svVEGF (snake venom VEGF) described in snake venoms. This is the pioneer review of svVEGF family, exploring its distribution among the snake venoms, molecular structure, main functions, and potential applications., (Copyright © 2021. Published by Elsevier Ltd.)

Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. MCs produce angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (ANGPTs). Serum concentrations of VEGF-A, VEGF-C, VEGF-D, ANGPT1 and ANGPT2 were determined in 64 mastocytosis patients and 64 healthy controls. Intracellular concentrations and spontaneous release of these mediators were evaluated in the mast cell lines ROSA KIT WT and ROSA KIT D816V and in human lung mast cells (HLMCs). VEGF-A, ANGPT1, ANGPT2 and VEGF-C concentrations were higher in mastocytosis patients compared to controls. The VEGF-A, ANGPT2 and VEGF-C concentrations were correlated with the symptom severity. ANGPT1 concentrations were increased in all patients compared to controls. ANGPT2 levels were correlated with severity of clinical variants and with tryptase levels. VEGF-A, ANGPT1 and VEGF-C did not differ between indolent and advanced mastocytosis. ROSA KIT WT , ROSA KIT D816V and HLMCs contained and spontaneously released VEGFs and ANGPTs. Serum concentrations of VEGFs and ANGPTs are altered in mastocytosis patients.

Background: The most common glomerular disease in children is nephrotic syndrome. Steroid-resistant nephrotic syndrome tends to have a worse disease course, which bears a significant risk of chronic kidney disease in children., Objective: To compare VEGF and neopterin levels between children with steroid-sensitive nephrotic syndrome (SSNS), steroid-resistant nephrotic syndrome (SRNS), and also healthy (control) children., Methods: This cross-sectional study was conducted at H. Adam Malik General Hospital, Indonesia from January to December 2018. There were 160 children aged 1 to 8 years with confirmed nephrotic syndrome and without end-stage renal disease and systemic diseases, divided into SSNS, SRNS, and control groups. Data regarding age, gender, urine albumin creatinine ratio (UACR), serum albumin, total cholesterol, urea, creatinine, VEGF, and neopterin levels were collected. A p-value of less than 0.05 is considered statistically significant., Results: There were no differences between groups in gender (p = 0.269) and age (p = 0.375), but there was significant difference of UACR, albumin level, total cholesterol level, and VEGF level between groups, (all p< 0.001). There was a moderate positive correlation between VEGF level and UACR (r(158) = 0.439, p< 0.001) and a moderate negative correlation between neopterin level and albumin level (r(158)= -0.312, p = 0.005)., Conclusion: There were no differences in serum VEGF and neopterin levels between steroid-sensitive and steroid-resistant nephrotic syndrome groups. Serum VEGF level was positively correlated with UACR while serum neopterin level was negatively correlated with serum albumin level., Competing Interests: There are no conflicts of interest., (© 2021 Riska Habriel Ruslie, Darmadi Darmadi, Gontar Alamsyah Siregar.)

Treatments enhancing angiogenesis for chronic cerebral hypoperfusion (CCH) are still in the research stage. Although encephalomyosynangiosis (EMS) is a common indirect anastomosis for the treatment of CCH, the effectiveness to promote angiogenesis is not satisfactory. Vascular endothelial growth factors (VEGF) is a cytokine found to specifically act directly on vascular endothelial cells, promote neovascularization, and enhance capillary permeability. However, the short half life and unstable property of VEGF underlies the need to explore available delivery system. In this study, poly (lactide-co-glycolide) (PLGA) was used to prepare VEGF controlled-release microspheres. In vitro and in vivo analysis of release kinetics showed that the microspheres could release VEGF continuously within 30 days. Then, modified chronic cerebral hypoperfusion rat model was established by ligation of bilateral internal carotid artery and one vertebral artery. At 14 days after ischemia, the EMS and the VEGF microspheres injection were performed. At 30 days after the injection, the result of Morris water maze displayed that combinating VEGF microspheres and EMS significantly ameliorated cognitive deficit after ischemia. We observed that combinating VEGF microspheres and EMS could further significantly increase cerebral blood flow. We speculated that this enhancement of cerebral blood flow was attributed to more angiogenesis induced by combination of VEGF microspheres and EMS, which verified by more collateral circulation with cerebral angiography and higher expression of CD31 or α-SMA. Our study demonstrated that combinating VEGF-PLGA controlled-release microspheres could significantly promote angiogenesis in EMS-based CCH rats model, providing new ideas for clinical treatment of CCH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: To evaluate the safety and impact on visual acuity, retinal and choroidal morphology of simultaneous cataract surgery and intravitreal anti-vascular endothelial growth factor on patients with visually significant cataracts and previously treated exudative age-related macular degeneration., Material and Methods: Prospective study, which included 21 eyes of 20 patients with exudative age-related macular degeneration submitted to simultaneous phacoemulsification and intravitreal ranibizumab or bevacizumab. The patients were followed for 12 months after surgery using a pro re nata strategy. Visual acuity, foveal and choroidal thickness changes were evaluated 1, 6 and 12 months post-operatively., Results: There was a statistically significant increase in mean visual acuity at one (13.4 letters, p < 0.05), six (11.5 letters, p < 0.05) and twelve months (11.3 letters, p < 0.05) without significant changes in retinal or choroidal morphology. At 12 months, 86% of eyes were able to maintain visual acuity improvement. There were no significant differences between the two anti-vascular endothelial growth factor drugs and no complications developed during follow-up., Discussion: Simultaneous phacoemulsification and intravitreal anti- vascular endothelial growth factor is safe and allows improvement in visual acuity in patients with visually significant cataracts and exudative age-related macular degeneration. Visual acuity gains were maintained with a pro re nata strategy showing that in this subset of patients, phacoemulsification may be beneficial., Conclusion: Cataract surgery and simultaneous anti-vascular endothelial growth factor therapy improves visual acuity in patients with exudative age-related macular degeneration.

Competing Interests: Conflict-of-interest disclosure: The author declares no competing financial interests.

Russian and foreign literature sources on vascular endothelial growth factors (VEGF) from different parts of the human body, their prevalence and involvement in pathological processes were analyzed. A conclusion has been drawn that further research on different types of VEGF is needed.

Background: Treatment of ischemic heart disease (IHD) remains a worldwide problem. Gene therapy, and recently, cell transplantation, have made desirable progress. A combination of appropriate stem cells and angiogenic genes appears promising in treating IHD., Objective: To study the results of angiogenesis and myogenesis induced by transplantation of the adenovirus carrying human vascular endothelial growth factor 165 (Ad-hVEGF(165))-transfected mesenchymal stem cells (MSCs) in IHD compared with direct MSC transplantation or Ad-hVEGF165 delivery., Methods: Cultured MSCs were transfected by Ad-hVEGF(165), and secreted VEGF was measured by ELISA in vitro. Ad-hVEGF(165)-transfected MSCs (MSC/VEGF group), MSCs (MSC group), Ad-hVEGF(165) (VEGF group) or a serum-free medium (control group) was injected into syngeneic Wistar rats immediately after left coronary artery occlusion. All cells were marked with CM-DiI (Molecular Probes, USA) before transplantation. One week after treatment, messenger RNA expression of hVEGF(165) in the MSC/VEGF group was found to be significantly higher than in other groups by reverse transcriptase-polymerase chain reaction analysis. One month after cell transplantation, left ventricular (LV) ejection fraction, capillary density of the infarcted region, infarct size and hemodynamic parameters (including LV end-diastolic pressure, LV+dP/dt and LV-dP/dt) were measured and immunohistochemical analysis was performed., Results: A high level of VEGF was expressed by Ad-hVEGF(165)-transfected MSCs. LV ejection fraction, mean capillary density of the infarcted region and hemodynamic parameters were significantly improved in the MSC/VEGF group compared with the MSC group, the VEGF group and the control group (P<0.001 for all). Partly transplanted MSCs showed the cardiomyocyte phenotype, expressed desmin and cardiac troponin T, and resulted in angiogenesis in the ischemic myocardium. However, a few transplanted MSCs incorporated into the vascular structure and most of the new vascular components were host-derived., Conclusions: The combined strategy of MSC transplantation and VEGF gene therapy can produce effective myogenesis and host-derived angiogenesis, resulting in the prevention of progressive heart dysfunction after myocardial infarction.

VEGF signaling often represents a critical rate-limiting step in physiological angiogenesis. The VEGF family comprises seven secreted glycoproteins that are designated VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, placental growth factor (PlGF) and VEGF-F. The VEGF family members bind their cognate receptors. The receptors identified so far are designated VEGFR-1, VEGFR-2, VEGFR-3 and the neuropilins (NP-1 and NP-2). We review in this article the biology of the VEGF ligands and the receptors.

Objectives: We sought to clarify the mechanism for neovascularization by ultrasonic microbubble destruction (US/MB) and its ability to improve the function of ischemic limbs., Background: In tissue, US/MB can cause capillary rupture, leading to angiogenesis and arteriogenesis., Methods: Seven days after removal of the femoral artery (day 0) in mice, microbubble/ultrasound treatment was performed by intermittent insonation (1.6 MHz, mechanical index 1.1) to the ischemic limbs after intravenous infusion of phospholipid-stabilized microbubbles BR14 (US/MB group). Effects were compared with those in untreated mice with ischemic limbs (control group)., Results: Immunostaining of the treated muscles revealed a greater leukocyte (CD45-positive cell) count in the US/MB group on days 3 and 7. These cells included F4/80-positive cells (macrophages) and CD3-positive cells (T-lymphocytes), both of which were immunoreactive to vascular endothelial growth factor (VEGF) antibody. Muscular VEGF content by Western blotting was elevated in the US/MB group on day 3, which declined but remained greater until day 21. The US/MB group showed a greater capillary density by alkaline phosphatase stain on day 7 without further increase at day 21. Surface vascularity of the muscles and blood flow were greater in the US/MB group on day 7, which further increased by day 21. Moreover, the US/MB group showed a two-fold longer treadmill time compared with the untreated control group on day 21. None of these favorable effects were observed in mice treated with ultrasound only or microbubbles only., Conclusions: Ultrasonic destruction of microbubbles delivered to the ischemic limbs can recruit inflammatory cells producing VEGF, which is followed by neovascularization and functional improvement, and thus has a therapeutic potential.

Vasculogenesis-the formation of blood vessels de novo from endothelial cells-and angiogenesis-the process of blood vessel remodeling-are regulated by a number of signal transduction pathways, some specific to the vascular system and others used more broadly during embryogenesis. Recent evidence in both zebrafish and mouse suggests a role for Hedgehog (Hh) signaling in both vasculogenesis and angiogenesis. Hh signaling can target endothelial cells directly or can stimulate blood vessel support cells to produce vascular growth factors. Current studies are aimed at determining how the Hh cascade interacts with the other signaling pathways to promote vessel differentiation.

Objective: To investigate the impact of supragingival scaling on the clinical outcomes of subgingival instrumentation completed after 1 week. Method and materials: In 27 patients with Stage II and Stage III periodontitis, pairs of contralateral quadrants were randomly assigned into test group 1 (single sitting scaling and root planing) and test group 2 (supragingival scaling followed by subgingival instrumentation after lweek). Periodontal parameters were recorded at baseline, 2, 4, and 6months; Gingival crevicular fluid vascular endothelial growth factor (VEGF) estimation was done at baseline in both groups and 7 days after supragingival scaling in test group 2. Results: At 6 months, significantly better improvement in test group 1 at sites with periodontal probing depth (PPD)>5mm; (APPD = 2.32 mm vs 1.41 mm, P= .001; Aclinical attachmen level [CAL] = 2.34 mm vs 1.39 mm, P=.001) was observed. Supragingival scaling resulted in significant reduction in gingival crevicular fluid VEGF (42.46 to 27.88 pg/site) after lweek. Regression analysis explained 14% variance in VEGF to baseline PPD at sites with PPD>4 mm; and 21% variance in CAL improvement to VEGF at sites with PPD>5mm. The percentage of sites with PPD = 5 to 8 mm reachingthe clinical endpoint was 52% and 40%fortest group 1 and test group 2, respectively. Better results were noticed in bleeding on pocket probing-positive sites in both groups. Conclusion: The sites with PPD > 5 mm where supragingival scaling was followed by subgingival instrumentation after 1 weekresulted in less favourable treatment outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] Persistent inflammation and bacterial infection commonly occur during the wound healing process, necessitating urgent development of effective strategies for treating drug-resistant bacterial infections. In this study, bismuth vanadate (BiVO 4) was successfully synthesized as an antibacterial agent that promotes wound healing. Through In vitro antibacterial experiments, it was observed that the prepared BiVO 4 exhibited excellent performance in catalyzing H 2 O 2 to produce hydroxyl radicals (OH) at a lower concentration (0.2 mg mL−1), resulting in significant antibacterial effects against Gram-negative Extended-Spectrum β-Lactamases-Producing Escherichia coli (ESBL- E. coli) strains. Furthermore, biosafety tests, cell scratch experiments, and ESBL- E. coli infected wound rat model experiments demonstrated high biocompatibility of BiVO 4 with a cell survival rate exceeding 85 %. Additionally, BiVO 4 promoted the production of vascular endothelial growth factors and fibroblasts migration while contributing to collagen production, effectively facilitating immune reconstruction at the wound site. By integrating peroxidase (POD)-like under acidic conditions (pH 4) and catalase (CAT)-like catalytic activities at under neutral conditions (pH 7), BiVO 4 exhibited the ability to activate free radical sterilization and accelerate wound healing by activating O 2. Therefore, our findings provide evidence for a dual enzyme regulatory mechanism involving antibacterial properties and promotion of wound tissue reconstruction for potential application in both antibacterial treatment and wound healing. [ABSTRACT FROM AUTHOR]

Despite advancements in therapeutic agents for diabetic chronic wounds, challenges such as suboptimal bioavailability, intricate disease milieus, and inadequate delivery efficacy have impeded treatment outcomes. Here, ultrasound‐responsive hydrogel incorporated with heparin‐binding domain (HBD) peptide nanoparticles is developed to promote diabetic wound healing. HBD peptide, derived from von Willebrand Factor with angiogenic activity, are first engineered to self‐assemble into nanoparticles with enhanced biostability and bioavailability. Ultrasound responsive cargo release and hydrogel collapses are first verified through breakage of crosslinking. In addition, desired antioxidant and antibacterial activity of such hydrogel is observed. Moreover, the degradation of hydrogel under ultrasound stimulation into smaller fragments facilitated the deeper wound penetration of ≈400 µm depth. Complete wound closure is observed from diabetic mice with chronic wounds after being treated with the proposed hydrogel. In detail, in vivo studies revealed that hydrogels loaded with HBD peptide nanoparticles increased the levels of angiogenesis‐related growth factors (VEGF‐A, CD31, and α‐SMA) to effectively accelerate wound repair. Overall, this study demonstrates that ultrasound‐responsive HBD peptide hydrogel provides a synergistic therapeutic strategy for external biofilm elimination and internal effective delivery for diabetic wounds with biofilm infection. [ABSTRACT FROM AUTHOR]

The article discusses a study on the bioactive mediator profile of patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA) treated with mepolizumab. The research aimed to understand variations between patients with bronchial asthma (BA) and EGPA, as well as the mechanisms of action of glucocorticoid (GC) and mepolizumab therapy. The study found differences in protein levels between BA and EGPA, with specific proteins being elevated in EGPA cases. Additionally, the study highlighted the effects of GC treatment on EGPA and the additional changes induced by mepolizumab, suggesting a multifaceted role of IL-5 in the pathogenesis of EGPA. [Extracted from the article]

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Signaling pathways that link genetic sequence variants to clinically overt HCM and progression to severe forms of HCM remain unknown. The purpose of this study was to identify signaling pathways that are differentially regulated in HCM, using proteomic profiling of human myocardium, confirmed with transcriptomic profiling. In this multicenter case-control study, myocardial samples were obtained from cases with HCM and control subjects with nonfailing hearts. Proteomic profiling of 7,289 proteins from myocardial samples was performed using the SomaScan assay (SomaLogic). Pathway analysis of differentially expressed proteins was performed, using a false discovery rate <0.05. Pathway analysis of proteins whose concentrations correlated with clinical indicators of severe HCM (eg, reduced left ventricular ejection fraction, atrial fibrillation, and ventricular tachyarrhythmias) was also executed. Confirmatory analysis of differentially expressed genes was performed using myocardial transcriptomic profiling. The study included 99 HCM cases and 15 control subjects. Pathway analysis of differentially expressed proteins revealed dysregulation of the Ras–mitogen-activated protein kinase, ubiquitin-mediated proteolysis, angiogenesis-related (eg, hypoxia-inducible factor-1, vascular endothelial growth factor), and Hippo pathways. Pathways known to be dysregulated in HCM, including metabolic, inflammatory, and extracellular matrix pathways, were also dysregulated. Pathway analysis of proteins associated with clinical indicators of severe HCM and of differentially expressed genes supported these findings. The present study represents the most comprehensive (>7,000 proteins) and largest-scale (n = 99 HCM cases) proteomic profiling of human HCM myocardium to date. Proteomic profiling and confirmatory transcriptomic profiling elucidate dysregulation of both newly recognized (eg, Ras–mitogen-activated protein kinase) and known pathways associated with pathogenesis and progression to severe forms of HCM. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the influence of combining autologous platelet-rich gel (APG) with continuous vacuum-sealed drainage (CVSD) and the exogenous recombinant human acidic fibroblast growth factor (rh-aFGF) on the healing processes of diabetic foot ulcers (DFU). The primary objective is to elucidate the complex molecular mechanisms associated with DFU, providing innovative perspectives for its treatment. Methods: Ninety patients diagnosed with DFU were randomly allocated into three distinct groups. Group A underwent CVSD following wound cleansing to facilitate healing. In Group B, in addition to conventional treatment, negative pressure wound therapy was applied, and rh-aFGF was introduced into normal saline for lavage, building upon the procedures of Group A. Group C received APG along with the interventions applied in Group B. The clinical efficacy of each group was systematically observed and analyzed. Additionally, changes in plasma oxidative stress, inflammatory markers, vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) were assessed both before treatment and 14 days post-treatment. Results: Following treatment, all groups exhibited commendable clinical efficacy. Group C demonstrated a superior wound healing rate, reduced frequency of dressing changes, and shorter wound healing duration (P< 0.05). Compared to baseline measurements, the levels of superoxide dismutase and PEDF increased, while malondialdehyde, VEGF, interleukin-6, interleukin-8, and monocyte chemotactic factor MCP-1 decreased in the wound tissue across all groups. Notably, Group C showed the most significant improvement in clinical efficacy and fortification of molecular mechanisms against oxidative stress (all P< 0.05). Conclusions: The integrative therapeutic approach combining APG with CVSD and rh-aFGF demonstrates notable efficacy in advancing wound healing. This effectiveness is evident through the reduced frequency of dressing changes and alleviation of wound-related pain. Additionally, the treatment regimen improves the cure rate for challenging, refractory wounds. These favorable outcomes can be attributed to the reduction of oxidative stress levels, attenuation of the local inflammatory response, and the enhancement of the balance between PEDF and VEGF. [ABSTRACT FROM AUTHOR]

This study aims to repurpose sericin in combating non-small lung cancer cells (A549 and H460) by combining it with dactolisib or vitamin D to reduce the dose of dactolisib and boost the anticancer effectiveness of dactolisib and vitamin D. Therefore, the binding affinities of individual and combined drugs were examined using in silico and protein-protein interaction studies, targeting NF-κB, Cyclin D1, p-AKT, and VEGF1 proteins. The findings manifested remarkable affinities for combinatorial drugs compared to individual compounds. To substantiate these findings, the combined IC50 for each combination (sericin + dactolisib and sericin + vitamin D) were determined, reporting 31.9 and 41.8 µg/ml, respectively, against A549 cells and 47.9 and 55.3 µg/ml, respectively, against H460 cells. Furthermore, combination indices were assessed to lower the doses of each drug. Interestingly, in vitro results exhibited marked diminutions in NF-κB, Cyclin D1, p-AKT, and VEGF1 after treatment with sericin + dactolisib and sericin + vitamin D compared to control lung cancer cells and those treated with a single drug. Moreover, A549 and H460 cells treated with both combinations demonstrated augmented caspase-3 levels, implying substantial apoptotic activity. Altogether, these results accentuated the prospective implementation of sericin in combination with dactolisib and vitamin D at low doses to preclude lung cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) rates are continuing to rise and it remains the most common gynecologic cancer in the US. Existing diagnostic methods are invasive and can cause pain and anxiety. Hence, there is a need for less invasive diagnostics for early EC detection. The study objective was to evaluate the utility of growth factors collected through minimally invasive cervicovaginal lavage (CVL) sampling as diagnostic and prognostic biomarkers for EC. CVL samples from 192 individuals undergoing hysterectomy for benign or malignant conditions were collected and used to quantify the concentrations of 19 growth and angiogenic factors using multiplex immunoassays. Patients were categorized based on disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), and EC (n = 66). EC group was stratified into grade 1/2 endometrial endometrioid cancer (n = 53) and other EC subtypes (n = 13). Statistical associations were assessed using receiver operating characteristics, Spearman correlations and hierarchical clustering. Growth and angiogenic factors: angiopoietin-2, endoglin, fibroblast activation protein (FAP), melanoma inhibitory activity, and vascular endothelial growth factor-A (VEGF-A) were significantly (p < 0.0001) elevated in EC patients. A multivariate model combining 11 proteins with patient age and body mass index exhibited excellent discriminatory potential (area under curve = 0.918) for EC, with a specificity of 90.7% and a sensitivity of 87.8%. Moreover, angiopoietin-2, FAP and VEGF-A significantly (p < 0.05–0.001) associated with tumor grade, size, myometrial invasion, and mismatch repair status. Our results highlight the innovative use of growth and angiogenic factors collected through CVL sampling for the detecting endometrial cancer, showcasing not only their diagnostic potential but also their prognostic value. [ABSTRACT FROM AUTHOR]

Introduction: Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is widely used as a first-line treatment for metastatic colorectal cancer (mCRC), with hypertension being a common adverse effect. However, there is limited data on the predisposing factors contributing to bevacizumab-induced blood pressure (BP) elevation. This study aims to identify clinical risk factors associated with bevacizumab-related hypertension in patients with mCRC. Methods: This retrospective study included 178 patients treated between January and June 2020. Demographic data and medical histories were extracted from hospital electronic medical records. Results: Among the 178 patients, 54 (30.3%) developed bevacizumab-related hypertension, with a median onset time of 48 days. Univariate and multivariate analyses identified pre-existing hypertension [odds ratio (OR), 3.30; 95% confidence interval (CI), 1.56–6.99] and age ≥60 years (OR, 2.04; 95% CI, 1.00–4.17) as independent risk factors for bevacizumab-related hypertension. The area under the receiver operating characteristic (ROC) curve was 0.66 (95% CI, 0.57–0.75, P < 0.001). The median overall survival (OS) for the cohort was 30.53 months (95% CI, 22.23–38.84). No significant differences in OS were observed between patients with and without bevacizumab-related hypertension (31.13 vs. 27.87 months, P = 0.86). Conclusion: Pre-existing hypertension and age ≥60 years are significant clinical risk factors for bevacizumab-related hypertension in mCRC patients. Bevacizumab-related hypertension did not affect overall survival. Clinicians should closely monitor BP within the first 2 months of bevacizumab treatment in high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Gastrodia elata Blume, also called Tian Ma (TM), has been used to treat stroke for centuries. However, its effects on inflammation in acute cerebral ischemic injury and underlying mechanisms involved in microglial polarization remain unknown. The present study explored the effects of the TM extract on the modulation of microglial M1/M2 polarization 2 days after transient cerebral ischemia. Methods: Male Sprague Dawley rats were intracerebroventricularly administered with 1% dimethyl sulfoxide 25 min before cerebral ischemia and subsequently intraperitoneally administered 0.25 g/kg (DO + TM-0.25 g), 0.5 g/kg (DO + TM-0.5 g), or 1 g/kg (DO + TM-1 g) of the TM extract after cerebral ischemia onset. Results: DO + TM-0.5 g and DO + TM-1 g treatments downregulated the following: phospho-c-Jun N-terminal kinase (p-JNK)/JNK, tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3), TRAF3-interacting JNK-activating modulator (T3JAM), p-nuclear factor-kappa B p65 (p-NF-κB p65)/NF-κB p65, ionized calcium-binding adapter molecule 1 (Iba1), CD86, TNF-α, interleukin (IL)-1β, and IL-6 expression and toll-like receptor 4 (TLR4)/Iba1, CD86/Iba1, and p-NF-κB p65/Iba1 coexpression. These treatments also upregulated IL-10, nerve growth factor, and vascular endothelial growth factor A expression and YM-1/2/Iba1 and IL-10/neuronal nuclei coexpression in the cortical ischemic rim. The JNK inhibitor SP600125 exerted similar treatment effects as the DO + TM-0.5 g and DO + TM-1 g treatments. Conclusion: DO + TM-0.5 g and DO + TM-1 g/kg treatments attenuate cerebral infarction by inhibiting JNK-mediated signaling. TM likely exerts the neuroprotective effects of promoting M1 to M2 microglial polarization by inhibiting JNK/TLR4/T3JAM/NF-κB-mediated signaling in the cortical ischemic rim 2 days after transient cerebral ischemia. [ABSTRACT FROM AUTHOR]

Introduction: Emerging evidence suggests that psoriasis and periodontitis are linked via systemic inflammation. However, the role of angiogenesis as an additional connecting mechanism between these diseases remains unclear. Methods: This case control study explored the effect of psoriasis on the gingival crevicular fluid (GCF) levels of vascular endothelial growth factor A (VEGF-A) in patients with different stages of periodontitis. Thirty-one patients with psoriasis (P) and thirty healthy controls (C) underwent physical and intraoral evaluations, with diagnoses confirmed by dermatologists and periodontists. GCF VEGF-A was measured using a multiplex-bead immunoassay. Statistical analyses included Fisher exact tests, Student's T-tests, linear regression models, and mediation analyses. Results: Psoriasis patients had significantly lower GCF VEGF-A levels compared to controls (p =0.008). Psoriasis was negatively associated with GCF VEGF-A (p =0.006), while severe periodontitis was positively associated with GCF VEGF-A levels, regardless of tobacco use (p =0.027). Further analyses revealed that severe periodontitis significantly increased GCF VEGF-A levels only in the C group (p =0.038), but not in psoriasis patients (p >0.610). Mediation analyses confirmed a significant direct and total effect of psoriasis on GCF VEGF-A (p >0.002), with no significant indirect effect through periodontitis (p =0.699). Discussion: Psoriasis and severe periodontitis are associated with GCF levels of VEGF-A in opposite and independent ways. In subjects with psoriasis, the impact of the dermatosis is direct with no mediation from periodontitis. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to prepare cholesterol and stearic acid-based solid lipid nanoparticles of gabapentin (GAB-SLNs) for protection against streptozotocin (STZ)-induced retinal injury in rats. Methods: We prepared four preparations of GAB-SLNs using a hot high-shear homogenization ultrasonication process, and the best formulation was selected and tested for biological activity. The retinal injury was brought in male adult albino rats while gabapentin doses continued for 6 weeks. Six groups of rats were assigned as the vehicle, diabetic, diabetic + gabapentin (10–20 mg/kg), and diabetic + GAB-SLNs (10–20 mg/kg). GAB-SLN#2 was selected as the optimized formulation with high entrapment efficacy (EE%, 98.64% ± 1.97%), small particle size (185.65 ± 2.41 nm), high negative Zeta potential (−32.18 ± 0.98 mV), low polydispersity index (0.28 ± 0.02), and elevated drug release (99.27% ± 3.48%). The TEM image of GAB-SLN#2 revealed a smooth surface with a spherical shape. Results: GAB-SLNs provided greater protection against retinal injury than free gabapentin as indicated by the histopathology data which demonstrated more organization of retinal layers and less degeneration in ganglion cell layer in rats treated with GAB-SLN#2. Further, GAB-SLN#2 reduced the inflammatory proteins (IL-6/JAK2/STAT3) and vascular endothelial growth factor (VEGF). Conclusion: The preparation of GAB-SLNs enhanced the physical properties of gabapentin and improved its biological activity as a neuroprotectant. Further studies are warranted to validate this technique for the use of oral gabapentin in other neurological disorders. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Materials and Methods Results Conclusion This study aimed to investigate the hypoxic changes in periodontal tissues resulting from smoking and periodontitis by assessing levels of hypoxia‐inducible factors (HIF‐1α, HIF‐2α, HIF‐3α) and vascular endothelial growth factor (VEGF) in gingival crevicular fluid (GCF).The study comprised 22 periodontally healthy non‐smokers (Group H), 22 periodontally healthy smokers (Group HS), 22 non‐smokers with periodontitis (Group P) and 22 smokers with periodontitis (Group PS). Clinical periodontal parameters were documented, and GCF samples were collected and analysed using enzyme‐linked immunosorbent assay (ELISA).Significantly elevated levels of HIF‐1α, HIF‐3α and VEGF were observed in Groups HS, P and PS compared to Group H (p < 0.05). Moreover, higher HIF‐2α levels were detected in the Groups HS and P compared to Group H (p < 0.05). Significant correlations were detected between all evaluated hypoxia biomarkers in the Group P (p < 0.05) except HIF‐2α and HIF‐3α. However, in the PS group, significant correlation appeared only between HIF‐1α and HIF‐2α (p < 0.05).Our findings indicate that smoking and periodontitis induce comparable hypoxic effects in periodontal tissues, as evidenced by the evaluated biomarkers. Further research is warranted to gain a deeper understanding of the mechanisms underlying hypoxia in periodontal tissues. [ABSTRACT FROM AUTHOR]

Ionising radiation (IR) is a form of energy that travels as electromagnetic waves or particles. While it is vital in medical and occupational health settings, IR can also damage DNA, leading to mutations, chromosomal aberrations, and transcriptional changes that disrupt the functions of certain cell regulators, genes, and transcription factors. These disruptions can alter functions critical for cancer development, progression, and treatment response. Additionally, IR can affect various cellular proteins and their regulators within different cell signalling pathways, resulting in physiological changes that may promote cancer development, progression, and resistance to treatment. Understanding these impacts is crucial for developing strategies to mitigate the harmful effects of IR exposure and improve cancer treatment outcomes. This review focuses on specific genes and protein biomarkers regulated in response to chronic IR exposure, and how their regulation impacts disease onset, progression, and treatment response. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to elucidate the differential immunological mechanisms and characteristics of hypertension induced by VEGF inhibitors (VEGFi) and VEGF receptor inhibitors (VEGFRi), with the goal of optimizing monitoring strategies and treatment protocols. Methods: We investigated the risk of immune-related adverse events associated with VEGFi/VEGFRi-induced hypertension by analyzing the FDA Adverse Event Reporting System (FAERS) database. Findings were corroborated with blood pressure characteristics observed in clinical patients and preclinical models exposed to various VEGF/VEGFRi. Clinical and preclinical studies were conducted to compare immunological responses and hypertension profiles between inhibitor classes. An integrative analysis across cancer types and species was performed, focusing on key signaling pathways. Results: Analysis of FAERS data, in conjunction with clinical observations, revealed that both VEGFi and VEGFRi significantly elevated the risk of immune-mediated, blood pressure-related adverse events (ROR=7.75, 95% CI: 7.76-7.95). Subsequent clinical and preclinical studies demonstrated differential immunological responses and hypertension profiles between inhibitor classes. VEGFRi exhibited a more rapid onset, greater blood pressure elevation, and higher incidence of immune-mediated adverse events compared to VEGFi (Systolic BP: ROR=0 for VEGFi vs. ROR=12.25, 95% CI: 6.54-22.96 for VEGFRi; Diastolic BP: ROR=5.09, 95% CI: 0.60-43.61 for VEGFi vs. ROR=12.90, 95% CI: 3.73-44.55 for VEGFRi). Integrative analysis across cancer types and species, focusing on key signaling pathways, revealed that VEGF/VEGFRi-induced blood pressure elevation was associated with immunomodulation of the mitogen activated protein kinase (MAPK) pathway (R=-0.379, P=0.0435), alterations in triglyceride metabolism (R=-0.664, P=0.0001), modulation of myo-inositol 1,4,5-trisphosphate-sensitive calcium release channel activity (R=0.389, P=0.0378), and dysregulation of nitric oxide eNOS activation and metabolism (R=-0.439, P=0.0179). Discussion: The temporal dynamics of these effects demonstrated greater significance than dose-dependent responses. Both VEGFi and VEGFRi significantly augmented the risk of immune-mediated, blood pressure-related adverse events, with VEGFRi inducing a more rapid and pronounced onset of blood pressure elevation and a higher incidence of immune-related, blood pressure-associated adverse events compared to VEGFi. [ABSTRACT FROM AUTHOR]

Introduction: Desmoid tumors (DT) are rare, locally invasive tumors originating from connective tissue. Surgical intervention is no longer the standard treatment for DT, as systemic therapy gradually replaces it due to its superior efficacy. Despite the availability of various treatment modalities, there is a need for a first-line systemic treatment regimen that offers both effective disease control and acceptable safety profiles. Methods: To assess the efficacy and safety of different systemic treatment agents for DT, we conducted a systematic review and network meta-analysis. Eligible studies were identified through searches of PubMed, Embase, and the Cochrane Library databases, and data were extracted according to predefined inclusion criteria. Results: Three articles and clinical data from 295 patients with progressive and refractory DT were included in this Bayesian network meta-analysis. When considered by objective response rate (ORR), the efficacy of γ-secretase inhibitor versus placebo (OR 0.12, 95%CI 0.01–1.68) is superior to that of TKI (OR 0.49, 95%CI 0.03–7.62) and chemotherapy (OR 0.90, 95%CI 0.02–40.00). Vascular endothelial growth factor (VEGF)-TKI (OR, 0.09; 95% CI, 0.01–1.79) seemed to have the highest improvement in terms of 1-yr PFS rate, while chemotherapy seemed to have the highest improvement across all therapies in terms of 2-yr PFS rate across all therapies (OR, 0.06; 95 percent CI, 0.01–2.98). In terms of safety, the incidence of AEs is highest for γ-secretase inhibitor versus placebo (OR 0.16, 95%CI 0.02–1.55), while TKI is associated with the least AEs (OR 0.62, 95%CI 0.06–6.97). Conclusion: γ-secretase inhibitor provides superior local control of tumors, while chemotherapy and TKI may offer better long-term survival benefits. Among the three regimens, TKI demonstrated better treatment-related safety. These findings have important implications for guiding clinical practice in systemic treatment of DT. Highlights: The study conducted a systematic review and Bayesian network meta-analysis to evaluate the efficacy and safety of systemic treatment options for progressive and refractory desmoid tumors. The analysis included 3 RCT studies, and the primary clinical endpoints were progression-free survival and objective response rate. The network meta-analysis showed that γ-secretase inhibitors have better tumor response and more severe toxicity, while chemotherapy and TKI may have better long-term survival benefits. [ABSTRACT FROM AUTHOR]

The article discusses the use of polynucleotides, derived from salmon DNA, in skin regeneration and repair. Polynucleotides have shown efficacy in promoting wound healing, tissue regeneration, and reducing inflammation by activating dermal fibroblasts and enhancing collagen production. The mechanism of action involves targeting the Adenosine A2A receptor and utilizing the salvage pathway for DNA repair. While promising, further clinical studies are needed to fully understand the potential benefits and risks of polynucleotide use in skincare. [Extracted from the article]

Introduction: The bone marrow examination is an essential investigation in the diagnosis and management of many haematological disorders. The integration of all investigations, including peripheral blood analysis, bone marrow aspirate, and trephine biopsy findings, along with supplementary tests such as immunophenotyping, cytogenetic analysis, and molecular genetic studies, is crucial for arriving at a final diagnosis. Aim: To assess the presence of reticulin fibres in bone marrow biopsy sections in haematological malignancies, to evaluate the grade of BMF associated with haematological malignancies and to assess the role of angiogenesis using IHC markers in various haematological malignancies. Materials and Methods: A cross-sectional study was conducted in the Department of Pathology at the National Institute of Pathology, Safdarjung Hospital, New Delhi, India in 2009 for a duration of 18 months. Thirty-eight patients with a diagnosis of Acute Myeloid Leukaemia (AML), Acute Lymphoblastic Leukaemia (ALL), Chronic Myeloid Leukaemia (CML), and Chronic Lymphoproliferative Disorder (CLPD) were studied. Bone marrow biopsies were taken, fixed in 10% formalin, and decalcified in 10% Ethylene Diamine Tetraacetic Acid (EDTA). Routine paraffin embedding was performed, and serial sections of 4 µm were obtained on poly-L-lysine-coated slides for Immunohistochemistry (IHC) {Vimentin, Vascular Endothelial Growth Factor (VEGF), CD-34, Smooth Muscle Actin (SMA)}. The presence of reticulin fibres in the bone marrow biopsy sections was assessed using two special stains: Gomori's Silver Impregnation and Masson's Trichrome. Fibrosis was quantified according to the Baurmeister 0-4 grading system of Bone Marrow Fibrosis (BMF). Results: The results of the present study suggest that Endothelial to Mesenchymal Transition (EndMT) may play a role in the pathogenesis of BMF. Various grades of fibrosis were observed, with 15 cases (39.47%) in Grade 3, followed by 11 cases (28.95%) in Grade 2, 8 cases (21.05%) in Grade 1, and 4 cases (10.53%) in Grade 4. Conclusion: BMF was a significant finding even in the early stages of the majority of the lesions studied and was closely linked with angiogenesis. This study showed that angiogenesis plays an important role in the pathogenesis of haematological neoplasms and that VEGF is a prominent stimulus in the majority of these disorders. Additionally, this study suggests that EndMT has a possible role in the pathogenesis of BMF. [ABSTRACT FROM AUTHOR]

The article in the JNCI: Journal of the National Cancer Institute celebrates Glenn Algire's 1945 pioneering contribution to antiangiogenic therapy for cancer. Algire's observations on tumor angiogenesis laid the foundation for Judah Folkman's idea in 1971 that angiogenesis inhibitors could be used to treat cancer. The article discusses the development of VEGF inhibitors and other antiangiogenic drugs, as well as the challenges and potential future directions in antiangiogenic cancer therapy. It emphasizes the complexity of tumor angiogenesis regulation and the need to explore new strategies beyond VEGF-targeted therapies to improve efficacy in cancer treatment. [Extracted from the article]

Introduction: The expression of alpha-five beta-three (αVβ3) integrins is upregulated in various malignancies undergoing angiogenesis. The development of integrin antagonists as diagnostic probes makes the αVβ3 integrin a suitable candidate for targeting tumor angiogenesis. The goal of this study was to optimize the radiolabeling and evaluate the potential of conjugated integrin antagonist carbamate (IAC), a peptidomimetic, as a theranostic radiopharmaceutical for targeting tumor angiogenesis. Methodology: Radiolabeling of DOTAGA [2,2′,2"–{10-(2,6-dioxotetrahydro-2H-pyran-3-yl)−1,4,7,10-tetraazacyclododecane-1,4,7-triyl} triacetic-acid]-IAC with [68Ga]Ga, [177Lu]Lu, and [225Ac]Ac was optimized. The binding affinity (Kd) of DOTAGA-IAC for the αVβ3 receptor and cancer cell lines was quantified. The biodistribution studies were conducted in healthy Wistar rats. Dosimetry analysis was performed on [177Lu]Lu-DOTAGA-IAC distribution data. A pilot study of [68Ga]Ga-DOTAGA-IAC and [18F]FDG Positron Emission Tomography (PET/CT) imaging was performed in five patients with histopathologically confirmed breast cancer. PET/CT findings were compared between [68Ga]Ga-DOTAGA-IAC and [18F]FDG in these patients. Results: Radiopharmaceuticals were prepared with high radiochemical purity (>99.9%). Kd and Bmax measurements were 15.02 nM and 417 fmol for αVβ3 receptor protein: 115.7 nM and 295.3 fmol for C6 glioma cells. Biodistribution studies in rats suggested the excretion via kidneys and partially through the hepatobiliary route. The effective dose of [177Lu]Lu-DOTAGA-IAC was found to be 0.17 mSv/MBq. The dynamic study in patients revealed the optimal imaging time to be 30–35 mins postadministration. Out of the cohort, [68Ga]Ga-DOTAGA-IAC detected the primary lesions in all five patients with a mean standard uptake value (SUVmax) of 3.94 ± 0.58 compared with [18F]FDG (SUVmax 13.8 ± 6.53). Conclusion: The study demonstrates that DOTAGA-IAC exhibits strong binding to αVβ3 integrin, positioning it as a promising PET agent for assessing primary and metastatic cancers. The outcomes from the pilot study suggest the potential of [68Ga]Ga-DOTAGA-IAC PET/CT in breast carcinoma diagnosis. While recognizing the theranostic potential of DOTAGA-IAC for αVβ3 integrin-expressing tumors, further clinical investigations are warranted to comprehensively assess therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Retinal vascular diseases encompass several retinal disorders, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and retinal vascular occlusion; these disorders are classified as similar groups of disorders due to impaired retinal vascularization. The aim of this review is to address the main signaling pathways involved in the pathogenesis of retinal vascular diseases and to identify crucial molecules and the importance of their interactions. Vascular endothelial growth factor (VEGF) is recognized as a crucial and central molecule in abnormal neovascularization and a key phenomenon in retinal vascular occlusion; thus, anti-VEGF therapy is now the most successful form of treatment for these disorders. Interaction between angiopoietin 2 and the Tie2 receptor results in aberrant Tie2 signaling, resulting in loss of pericytes, neovascularization, and inflammation. Notch signaling and hypoxia-inducible factors in ischemic conditions induce pathological neovascularization and disruption of the blood–retina barrier. An increase in the pro-inflammatory cytokines—TNF-α, IL-1β, and IL-6—and activation of microglia create a persistent inflammatory milieu that promotes breakage of the blood–retinal barrier and neovascularization. Toll-like receptor signaling and nuclear factor-kappa B are important factors in the dysregulation of the immune response in retinal vascular diseases. Increased production of reactive oxygen species and oxidative damage follow inflammation and together create a vicious cycle because each factor amplifies the other. Understanding the complex interplay among various signaling pathways, signaling cascades, and molecules enables the development of new and more successful therapeutic options. [ABSTRACT FROM AUTHOR]

Inflammation has been recognized as major factor for successful bone regeneration. On the other hand, a prolonged or overshooting inflammatory response can also cause fracture healing failure. The nucleotide-binding oligomerization domain (NOD)-like receptor protein (NLRP)3 inflammasome plays a crucial role in inflammatory cytokine production. However, its role during fracture repair remains elusive. We investigated the effects of Nlrp3 deficiency on the healing of closed femoral fractures in Nlrp3−/− and wildtype mice. The callus tissue was analyzed by means of X-ray, biomechanics, µCT and histology, as well as immunohistochemistry and Western blotting at 2 and 5 weeks after surgery. We found a significantly reduced trabecular thickness at 2 weeks after fracture in the Nlrp3−/− mice when compared to the wildtype animals. However, the amount of bone tissue did not differ between the two groups. Additional immunohistochemical analyses showed a reduced number of CD68-positive macrophages within the callus tissue of the Nlrp3−/− mice at 2 weeks after fracture, whereas the number of myeloperoxidase (MPO)-positive granulocytes was increased. Moreover, we detected a significantly lower expression of vascular endothelial growth factor (VEGF) and a reduced number of microvessels in the Nlrp3−/− mice. The expression of the absent in melanoma (AIM)2 inflammasome was increased more than 2-fold in the Nlrp3−/− mice, whereas the expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 was not affected. Our results demonstrate that Nlrp3 deficiency does not markedly affect femoral fracture healing in mice. This is most likely due to the unaltered expression of pro-inflammatory cytokines and pro-osteogenic growth factors. [ABSTRACT FROM AUTHOR]

Angiogenesis, a vital physiological or pathological process regulated by complex molecular networks, is widely implicated in organismal development and the pathogenesis of various diseases. SIRT7, a member of the Sirtuin family of nicotinamide adenine dinucleotide + (NAD+) dependent deacetylases, plays crucial roles in cellular processes such as transcriptional regulation, cell metabolism, cell proliferation, and genome stability maintenance. Characterized by its enzymatic activities, SIRT7 targets an array of substrates, several of which exert regulatory effects on angiogenesis. Experimental evidence from in vitro and in vivo studies consistently demonstrates the effects of SIRT7 in modulating angiogenesis, mediated through various molecular mechanisms. Consequently, understanding the regulatory role of SIRT7 in angiogenesis holds significant promise, offering novel avenues for therapeutic interventions targeting either SIRT7 or angiogenesis. This review delineates the putative molecular mechanisms by which SIRT7 regulates angiogenesis, taking its substrates as a clue, endeavoring to elucidate experimental observations by integrating knowledge of SIRT7 substrates and established angiogenenic mechanisms. [ABSTRACT FROM AUTHOR]

The development of effective biomaterials for tissue regeneration has led to the exploration of blood derivatives such as leucocyte- and platelet-rich fibrin (L-PRF). A novel variant, Albumin-Enriched Platelet-Rich Fibrin (Alb-PRF), has been introduced to improve structural stability and bioactivity, making it a promising candidate for bone regeneration. This study aimed to evaluate Alb-PRF's capacity for cytokine and growth factor release, along with its effects on the proliferation, differentiation, and mineralization of human osteoblasts in vitro. Alb-PRF membranes were analyzed using histological, scanning electron microscopy, and fluorescence microscopy techniques. Cytokine and growth factor release was quantified over seven days, and osteoinductive potential was evaluated with MG-63 osteoblast-like cells. Structural analysis showed Alb-PRF as a biphasic, highly cellularized material that releases lower levels of inflammatory cytokines and higher concentrations of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) compared to L-PRF. Alb-PRF exhibited higher early alkaline phosphatase activity and in vitro mineralization (p < 0.05) and significantly increased the OPG/RANKL mRNA ratio (p < 0.05). These results indicate that Alb-PRF has promising potential as a scaffold for bone repair, warranting further in vivo and clinical assessments to confirm its suitability for clinical applications. [ABSTRACT FROM AUTHOR]

Rosa rugosa is a medicinal plant known for its potential anti-inflammatory, antioxidant, anti-cancer, and antimicrobial benefits. The pharmacological effects of Rosa rugosa extract on hair loss have not yet been documented. This research sought to assess the inhibitory effects and mechanisms of action of Rosa rugosa water extract (RWE) in a mouse model of dihydrotestosterone (DHT)-induced alopecia. The study was conducted using C57BL/6 mice, which were assigned to five groups: control, DHT-treated, Rosa rugosa water extract (RWE) at doses of 25 mg/kg and 100 mg/kg body weight, and bicalutamide-treated. To induce hair loss, dihydrotestosterone (1 mg/day per body weight) was administered via intraperitoneal injections, and dorsal hair removal was timed to align with the telogen phase. Each group received oral treatments for a period of 23 days. In this study, we assessed hair growth activity, examined histological changes, and performed immunoblot analysis. We noted improvements in hair length and thickness. Additionally, the protein expression of growth factors associated with hair growth, including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and insulin-like growth factor-1 (IGF-1), showed significant increases in the group treated with RWE. Additionally, treatment with RWE suppressed the protein expression of hair growth inhibitory factors, including dickkopf WNT signaling pathway inhibitor 1 (DKK1) and interleukin (IL)-6. Moreover, hair growth regulatory pathway related factors, including ERK, AKT, and GSK-3β, were activated. These findings indicate that RWE could serve as a promising natural therapy for preventing hair loss by enhancing the production of factors that promote hair growth while inhibiting those that suppress it. [ABSTRACT FROM AUTHOR]

Many types of viruses directly or indirectly target the vascular endothelial growth factor (VEGF) system, which is a central regulator of vasculogenesis and angiogenesis in physiological homeostasis, causing diverse pathologies. Other viruses have been developed into effective therapeutic tools for VEGF modulation in conditions such as cancer and eye diseases. Some viruses may alter the levels of VEGF in the pathogenesis of respiratory syndromes, or they may encode VEGF-like factors, promoting vascular disruption and angiogenesis to enable viruses' systemic spread. Oncogenic viruses may express interactive factors that perturb VEGF's functional levels or downstream signaling, which increases the neovascularization and metastasis of tumors. Furthermore, many viruses are being developed as therapeutic vectors for vascular pathologies in clinical trials. Major examples are those viral vectors that inhibit the role of VEGF in the neovascularization required for cancer progression; this is achieved through the induction of immune responses, by exposing specific peptides that block signaling or by expressing anti-VEGF and anti-VEGF receptor-neutralizing antibodies. Other viruses have been engineered into effective pro- or anti-angiogenesis multitarget vectors for neovascular eye diseases, paving the way for therapies with improved safety and minimal side effects. This article critically reviews the large body of literature on these issues, highlighting those contributions that describe the molecular mechanisms, thus expanding our understanding of the VEGF–virus interactions in disease and therapy. This could facilitate the clinical use of therapeutic virus vectors in precision medicine for the VEGF system. [ABSTRACT FROM AUTHOR]

Currently, approaches to personalized medicine are actively developing. For example, the use of platelet-rich plasma (PRP) is actively growing every year. As a result of activation, platelets release a wide range of growth factors, cytokines, chemokines, and angiogenic factors, after which these molecules regulate chemotaxis, inflammation, and vasomotor function and play a crucial role in restoring the integrity of damaged vascular walls, angiogenesis, and tissue regeneration. Due to these characteristics, PRP has a wide potential in regenerative medicine and gerontology. PRP products are actively used not only in esthetic medicine but also to stimulate tissue regeneration and relieve chronic inflammation. PRP therapy has a number of advantages, but the controversial results of clinical studies, a lack of standardization of the sample preparation of the material, and insufficient objective data on the evaluation of efficacy do not allow us to unambiguously look at the use of PRP for therapeutic purposes. In this review, we will examine the current clinical efficacy of PRP-based products and analyze the contribution of PRP in the therapy of diseases associated with aging. [ABSTRACT FROM AUTHOR]

Background: Neuropilin‐1 (NRP1) is expressed on the surface epithelium of respiratory tract and immune cells, demonstrating its possible function in regulating the immune response in airway disease. However, its role in patient with chronic rhinosinusitis (CRS) remains unknown. This study aimed to elucidate the role of NRP1 in CRS with nasal polyps (CRSwNP). Methods: Sinonasal biopsy specimens were immunohistochemically stained to investigate NRP1 expression. Double immunofluorescence, immunoblotting, and real‐time polymerase chain reaction were performed to evaluate NRP1 in primary human nasal epithelial cells (hNECs). An NRP1 inhibitor was administered to a murine nasal polyp (NP) model. Results: NRP1 was highly expressed in the epithelium in patients with CRSwNP compared to nasal tissue from controls and CRS without NP patients. NRP1 and vascular endothelial growth factor were upregulated in hNECs under hypoxia. Treatment with NRP1 inhibitor (EG00229) reduced the secretion of interleukin (IL)‐1β, IL‐6, IL‐8, and IL‐33 cytokines, as well as inducible nitric oxide synthase, cyclooxygenase‐2, and prostaglandin E2 in hNECs. We found that NRP1 was highly expressed in the airway epithelium in the murine NP model. The group treated with the NRP1 inhibitor had significantly fewer nasal polypoid lesions and reduced accumulations of immune cells. Conclusions: These findings reveal that NRP1 is upregulated in CRS and NP epithelium, and the inhibition of NRP1 may lead to a reduction in NP growth and immune cell infiltration. Our results suggest that NRP1 inhibition could be a novel possibility for treating nasal polyposis. [ABSTRACT FROM AUTHOR]

The editorial in the journal "Intensive Care Medicine" discusses the potential of therapeutic plasma exchange (TPE) as a treatment for septic shock, a condition with high mortality rates. TPE aims to restore immune balance and replace consumed protective plasma proteins in sepsis patients. While evidence from small studies suggests potential benefits of TPE, ongoing large-scale trials are needed to establish its effectiveness conclusively. The editorial highlights the importance of further research to determine the optimal use of TPE in septic shock patients. [Extracted from the article]

Many herbs have been shown to safely and successfully treat hyperlipidemia. However, the molecular mechanisms underlying their treatment remain unclear. In this study, 103 prescriptions for the treatment of hyperlipidemia containing 146 herbs were screened. Cluster analyses identified a core prescription comprising five herbs, namely, Crataegus pinnatifida (Shan Zha), Cassiae semen (Jue Ming Zi), Alisma orientale (Sam.) Juz. (Ze Xie), Salvia miltiorrhiza (Dan Shen), and RadixPolygoni Multiflori (He Shou Wu), in combination for the treatment of hyperlipidemia. Next, 9, 62, 5, 132, and 34 potential targets for each of the core herbs and a total of 512 hyperlipidemia-related protein targets were detected. Finally, 40 targets shared by core herbs and hyperlipidemia were identified. IL6, AKT1, IL1B, PTGS2, VEGFA, PPARG, and NOS3 were the seven proteins that were found to be most important in the treatment of hyperlipidemia. Interestingly, the Kyoto Encyclopedia of Genes and Genomes pathway indicated that these targets were mainly enriched in the lipid and atherosclerosis pathway and the cancer pathway. In addition, core target proteins such as AKT1, PTGS2, and PPARG have been demonstrated to play critical roles in hyperlipidemia and pancreatic cancer. Significant affinity between bioactive chemicals and proteins involved in cancer pathways was found by molecular docking. Molecular docking results showed that AKT1, PTGS2, and PPARG exhibited good binding ability with three bioactive chemicals, including 3-beta-hydroxymethyllenetanshiquinone, danshexinkum d, and physciondiglucoside. The treatment of hyperlipidemia by herbs may be mediated through the modulation of proteins associated with the cancer pathway. This study helps to provide a theoretical basis for future combined therapy for hyperlipidemia and cancer. [ABSTRACT FROM AUTHOR]

• Sclerocarya birrea fruit exocarp and Terminalia prunoides pods extracts have 24 poly phenolic metabolites including shikimic acid, gallic acid and quercetin-3-d-xyloside. • Sclerocarya birrea fruit exocarp, Terminalia prunoides extracts pod and their synergy inhibit the proliferation of HeLa cells. • Sclerocarya birrea fruit exocarp, Terminalia prunoides extracts pod and their synergy downregulate the expression of EGFR, VEGF, MACC1, and CYFRA 21-1 genes. • Sclerocarya birrea fruit exocarp, Terminalia prunoides extracts pod and their synergy downregulate the expression CD 95 gene. Cancer is one of the leading causes of death globally. Conventional drugs are expensive and have been reported to have side effects. This directs efforts in cancer research to search for inexpensive solutions with less or no side effects. This study aimed at screening for phytochemicals and the antiproliferative effects of Sclerocarya birrea fruit exocarp (SBFE) and Terminalia prunioides pods extracts (TPPE) on human cervical cancer cell line (HeLa). Extracts were qualitatively evaluated for their phytochemicals using HPLC and LC-MS/MS, and the antiproliferative effects by 4-[-3(4-Iodophenyl)-2-(4-nitro-phenyl)-2H-5-tetrazolio]-1,3-benzene sulfonate (WST-1) assay. HPLC and LC-MS/MS analysis led to identification and quantification of 24 polyphenolic metabolites amongst which shikimic acid (3.6014 mg g-1), gallic acid (40.8283 mg g-1), and quercetin-3-d-xyloside (3.4677 mg g-1) as the major metabolites. Results from antiproliferative effects of extracts were used to make 3 potential anticancer formulations. Furthermore, effects of extracts and formulations on the expressions of cervical cancer markers: Epidermal Growth Factor Receptor (EGFR), Metastasis-Associated in Colon Cancer 1 (MACC1), Vascular Endothelial Growth Factor (VEGF), Cytokeratin Fragment (CYFRA 21-1), and Cluster differentiation 95 (CD95) were evaluated by Reverse transcription quantitative Polymerase Chain Reaction (RT-qPCR). Methanol and ethyl acetate extracts of both plants tested positive for saponins, tannins, flavonoids, phenols, terpenoids, cardiac glycoside and steroids. Methanol extracts were the most effective with IC 50 values of 75 µg/mL and 190 µg/mL for SBFE and TPPE respectively. The formulations: M1E1M2E2 and M1M2 had IC 50 values of 77 µg/mL and 83 µg/mL respectively. All treatments downregulated mRNA expression of EGFR, VEGF, MACC1, CYFRA 21-1, and upregulated CD 95 mRNA expression. Formulations were more effective than individual extracts against HeLa cells. However, there is need for further testing for other possible mechanisms of action and isolation of phytocompounds. [ABSTRACT FROM AUTHOR]

Objective: Bone incision leads to interrupted and sluggish blood flow in the process of distraction osteogenesis (DO), creating a hypoxia (0–2% oxygen tension) at the center of the bone callus. This hypoxia is critical in the coupling of osteogenesis and angiogenesis during DO. This study aimed to investigate the effect of Uniaxial Static Strain (USS) on osteogenesis in osteoblasts under hypoxic conditions, with a focus on the expression of osteogenic markers and angiogenic factors. Methods: The USS was made by a multi-unit tension compression device.Osteoblasts were subjected to 10% USS made under hypoxic conditions to mimic the process of DO in vitro. The cell proliferation, alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of osteogenic and angiogenic markers were evaluated by using a CCK-8 assay, alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qRT-PCR, Western blotting and ELISA. Results: Hypoxia inhibited osteoblast cell proliferation, ALP activity, mineralized nodule formation, and the expression of runt-related transcription factor 2 (Runx- 2), osteopontin(OPN), osteocalcin (OCN), collagen type I (Col1a1). Conversely, hypoxia upregulated the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF), which are associated with angiogenesis. However, the application of USS enhanced osteoblasts' osteogenic capacity and upregulated angiogenic factors under hypoxic conditions. Conclusion: USS can enhance osteogenesis in osteoblasts under hypoxic conditions. Moreover, it may stimulate angiogenesis by promoting the expression of VEGF, which further contributes to bone formation. This finding provides important implications for understanding the mechanisms involved in bone regeneration and may have clinical applications in optimizing the effectiveness of DO techniques. [ABSTRACT FROM AUTHOR]

Objective: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence. Material and methods: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure. Results: Three hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58–0.68; specificity, 0.75–0.76). Conclusion: A multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation. Clinical relevance statement: A prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone. Key Points: Identification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation. This model for recurrence, incorporating many patient variables, had higher specificity than staging alone. Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules. [ABSTRACT FROM AUTHOR]