Increased Vascular Endothelial Growth Factor Expression Research Articles

Regulation role of miR-204 on SIRT1/VEGF in metabolic memory induced by high glucose in human retinal pigment epithelial cells.

To examine the regulatory role of microRNA-204 (miR-204) on silent information regulator 1 (SIRT1) and vascular endothelial growth factor (VEGF) under high-glucose-induced metabolic memory in human retinal pigment epithelial (hRPE) cells. Cells were cultured with either normal (5 mmol/L) or high D-glucose (25 mmol/L) concentrations for 8d to establish control and high-glucose groups, respectively. To induce metabolic memory, cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d. In addition, exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control, miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect miR-204 mRNA levels. SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot. Flow cytometry was used to investigate apoptosis rate. It was found that high glucose promoted miR-204 and VEGF expression, and inhibited SIRT1 activity, even after the return to normal glucose culture conditions. Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression. However, downregulation of miR-204 produced the opposite effects. The study identifies that miR-204 is the upstream target of SIRT1 and VEGF, and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.

The Effect of Gel Secretome Hypoxia Mesenchymal Stem Cells to Increase P38 and VEGF Expression in Rats’ Diabetic Wounds

Mesenchymal stem cells (MSCs) under hypoxic conditions can produce secretomes containing growth factors such as vascular endothelial growth factor (VEGF), accelerating angiogenesis in wound healing disorders in diabetic ulcers. This study aimed to prove the influence of gel secretome MSC hypoxia administration on increasing VEGF and P38 gene expression in rats’ diabetic wounds. An in vivo study was conducted on 25 male Rattus norvegicus, randomly divided into four groups: base gel as a negative control, Gentamycin as a positive control, and gel secretome at a dose of 100 µL, and 200 µL/kg body weight. The differences in P38 and VEGF gene expression were tested using quantitative real-time polymerase chain reaction (qRT-PCR). Wound closure appeared to be fastest in treatment groups at a dose of 100 µL/kg body weight, followed by a dose of 200 µL/kg body weight, followed by Gentamycin and base gel group. The wound closure rate percentage was significantly different in the intervention group compared to the control group (p = 0.000). The results showed a significant difference in P38 and VEGF gene expression between the treatment and control groups (p = 0.000). This study demonstrates the administration of gel secretome hypoxia mesenchymal stem cells increases P38 and VEGF expression in rats’ diabetic wounds.

The features of endometrial receptivity in women underwent in vitro fertilization procedure

The objective: to determine the endometrial receptivity markers in women who underwent the procedure of in vitro fertilization (IVF). Materials and methods. The study included 191 patients who applied to the reproductive department of Caspian International Hospital from 2020 to 2022 for an examination for infertility.The main group included 50 patients with infertility who underwent endometrial biopsy during the implantation window (7th–9th days after ovulation in the cycle preceding the IVF stage); the control group – 20 women who underwent treatment for male infertility with a positive program result.The patients underwent IVF according to the standard method. The following expression levels were determined: leukemia inhibiting factor (LIF); vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1). The percentage expression of area indices was estimated.Results. In the women of the main group absence of embryo transfer was in 5 (10%) cases, no pregnancy – 27 (54%) cases, presence of pregnancy – 23 (46%) cases, cycle disruption – 3 (6%) cases.According to the results of a histological examination in women of the control group, complete secretory transformation of the endometrium was determined in 85% of cases. In the main group complete secretory transformation of the endometrium was detected in 48%, defective secretory transformation – in 42%, morphological signs of endometrial changes corresponding to the average secretory phase of the cycle – in 10% of women.A significant decrease (p<0.001) in the expression of LIF in the histological structures (stroma) of the endometrium was revealed in the main study group compared to the control one. The most pronounced differences were observed in the expression level of TGF-β1 in the stroma (approximately 10-fold; p<0.001).Conclusions. Thus, infertile women who underwent IVF have multidirectional changes in endometrial receptivity markers: decrease in LIF expression in the stroma and epithelium, increase in VEGF expression in the stroma, and a significant increase in TGF-β1 expression in the stroma and epithelium. These changes indicate an abnormal functional state of the endometrium and affect the results of IVF in patients (absence of oocyte transfer and failure to conceive).

Validation of an enzyme-linked immunosorbent assay test-system for bevacizumab concentration determing in biological fluids

Introduction. One of the reasons for the development of many diseases primarily malignant is the increased expression of Vascular Endothelial Growth Factor (VEGF). Bevacizumab is a drug that neutralizes the biological activity of VEGF. The molecular structure of bevacizumab is a recombinant humanized antibody. Its use reduces vascularization in the foci of increased VEGF expression which slows down tumor growth and also helps restore vision in a number of ophthalmic diseases. To determine the concentration of bevacizumab in human biological fluids a test system based on Enzyme-linked Immunosorbent Assay (ELISA) is presented.Aim. Aim of this study is the validation of this test system.Materials and methods. Blank sera of volunteers, bevacizumab solution, enzyme-linked immunosorbent assay, solid-phase sandwich ELISA kit, microplate photometer.Results and discussion. The following characteristics of the test system were determined: the lower limit of quantification is 2.0 mcg/ml, the upper calibration range is up to 200 mcg/ml, the accuracy and precision within one series and between series does not exceed 20 %, and the total error of the method – 30 %, short-term stability for samples at room temperature – 6 hours, long-term stability – 14 days at –20 °C, the ability to freeze/thaw of samples is up to three times, the ability to determine samples with a concentration above the upper calibrator after diluting in 2 times.Conclusion. The results obtained fully comply with international acceptance criteria and allow the use of the ELISA test system manufactured by LLC "Probiotek" for use in the field of clinical laboratory diagnostics.

Selenium Deficiency Can Promote the Expression of VEGF and Inflammatory Factors in Cartilage Differentiation and Mediates Cartilage Injury.

Selenium plays a crucial role as a micronutrient, primarily exerting its biological functions through selenoproteins. It has been established that selenium deficiency adversely impacts cartilage development, leading to alterations in chondrocyte function. In regions with low selenium intake, endemic osteochondrosis has been documented, characterized by compromised growth plate and articular cartilage formation. Vascular endothelial growth factor (VEGF) stands out as a pivotal angiogenic factor, with elevated levels contributing significantly to vascular invasion into chondrocytes. This VEGF-mediated invasion serves as a key signal, prompting morphological changes in the growth plate and initiating cartilage remodeling. In animal models, the selenium deficiency group exhibited heightened levels of the cartilage damage marker matrix metalloproteinases 13 (MMP13). This resulted in articular cartilage degeneration, accompanied by a substantial increase in VEGF expression within the growth plate and articular cartilage, as compared to the normal group. In a chondrogenic progenitor cell (CPC) differentiation model, insufficient selenium induced chondrocyte damage and upregulated inflammatory factors such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX2). The selenium-deficient groups showed elevated expressions of VEGF, VEGFR2, MMP13, Collagen X, and Angiopoietin 1, accelerating the degradation of the extracellular matrix (ECM), which further promoted the development of cartilage-related diseases. Taken together, these findings provide novel insights for a better understanding of the role of low selenium in cartilage degeneration and angiogenesis. They shed light on the intricate influence of low selenium levels on the development of articular cartilage, emphasizing the interconnected pathways and processes involved.

The effects of prophylactic tadalafil use on VEGF expression in the rabbit model of steroid-induced femoral head avascular necrosis.

The purpose of this study was to examine the effect of prophylactic tadalafil use on a steroid-induced femoral head avascular necrosis model in terms of microscopic, imaging, and molecular biological changes. Twenty-four New Zealand rabbits were divided into 3 equal groups. Eight rabbits were designated as the control group and did not receive treatment. Rabbits in group 1 (G1) received 0.1 mg/kg Escherichia coli lipopolysaccharide (LPS) intravenously and 40 mg/ kg methylprednisolone sodium succinate (MP) was administered intramuscularly for 3 days consecutively. Rabbits in group 2 (G2) were given 5 mg/kg tadalafil orally for 10 consecutive days. Starting on the eighth day, 0.1 mg/kg LPS was given, and following this 40 mg/kg MP injections were administered for 3 days. All animals were sacrificed 3 weeks after the final MP injection. Magnetic resonance imaging was performed, and bilateral femora were harvested. Half of the femoral head was stored for Vascular Endothelial Growth Factor (VEGF) examination with Western blot analysis. The other half was examined microscopically for the presence of osteonecrosis. In G1, 15 out of 16 hips (93%) of the 8 rabbits had osteonecrosis compared to 8 out of 12 hips (67%) of 6 rabbits in G2 (P > .05). The VEGF expression in G2 was significantly higher than in the control group and G1 (P < .05 and P < .001, respectively). There was no significant difference in VEGF expression between the control group and G1 (P > .05). This study has shown us that femoral head osteonecrosis can be reliably induced with LPS and corticosteroid, as described in the literature. Prophylactic tadalafil use did not decrease the occurrence of osteonecrosis significantly. However, it significantly increased VEGF expression in the femoral head independent of the effects of steroids and LPS.

HMOX1 Participates in Pre-Eclampsia by Regulating the Proliferation, Apoptosis, and Angiogenesis Modulation Potential of Mesenchymal Stem Cells via VEGF.

Mesenchymal stem cells (MSCs) are involved in the pathogenesis of pre-eclampsia (PE). Heme oxygenase (HMOX) protects against placental cytotoxic injuries associated with PE. Here, we aimed to clarify the roles of HMOX1 in MSC proliferation and apoptosis, trophoblast cell migration, and regulation of angiogenesis, and assess its involvement in the pathogenesis of PE. HMOX1 and vascular endothelial growth factor (VEGF) expression levels in decidual tissues and decidua-derived MSCs (dMSCs) of healthy pregnant women and patients with PE were evaluated via quantitative reverse transcription-polymerase chain reaction and western blotting. Moreover, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were used to analyze the cell viability, apoptosis, and migration, respectively. The tube formation ability of human umbilical vein endothelial cells (HUVECs) was also evaluated. Compared to the healthy pregnant women, HMOX1 expression was upregulated in the decidual tissue and downregulated in the dMSCs of patients with PE. HMOX1 overexpression significantly increased dMSC proliferation, decreased cell apoptosis, and increased VEGF expression. Moreover, HMOX1-plasmid transfected dMSC culture supernatant promoted the migration of HTR-8/SVneo cells and improved angiogenesis by HUVECs. The opposite effects were observed in HMOX1-small interfering RNA-treated dMSCs cells. However, VEGF-siRNA reversed the effects of HMOX1-plasmid. HMOX1 is involved in the pathogenesis of PE by regulating the proliferation, apoptosis, and angiogenesis modulation potential of MSCs via VEGF, acting as a potential therapeutic target for PE.

Analysis of Histological Prognostic Factors in Colorectal Carcinoma and Relationship of VEGF and E-Cadherin Expression in Prognostic Assessment

Colorectal carcinomas (CRC) are associated with several histopathological and molecular factors of prognostic and hence therapeutic implications, including for epithelial mesenchymal transition (EMT) and angiogenesis. Downregulation of E-cadherin is a crucial step in EMT, directly related to tumor progression, invasion, and metastasis. Vascular endothelial growth factor (VEGF) induces angiogenesis and thereby tumour progression and metastases. Our objective was to analyse VEGF and E-cadherin expression in patients with CRC and to effectively assess the relationship of these with histopathological factors. 50 cases of CRC obtained over eighteen months duration, were included in the study. Haematoxylin and Eosin-stained sections were studied for histopathological factors. Immunohistochemistry with E-Cadherin and VEGF were performed on representative sections and evaluated. Histopathological features of importance noted were low grade tumour budding (55.5%), Infiltrative invasive front (83%), lympho-vascular invasion (50%). Preserved expression of E-Cadherin was seen in 66% of the cases, and 34% reduced expression, predominantly noted in patients above the age of 50, increased tumour size, mucinous variants, advanced TNM stage, lymph node involvement and high-grade tumour budding. VEGF staining was seen in 64% of the cases with varying intensity. Increased VEGF expression was noted in poorly differentiated tumours, advanced Duke’s stage and with lymph node metastasis. Colorectal carcinomas with high grade tumour budding were associated with lymph vascular invasion, infiltrative invasive front and significantly correlated with TNM stage. High grade tumours and adverse histopathological prognostic factors revealed a reduced E-cadherin expression and increased VEGF expression.

1491-P: ER Stress Drives the VEGF Expression in Monocytic Cells by Mechanisms Involving CHOP/ROS/HIF-1alpha/NRF2 and NF-kappaB/p38 MAPK Pathways

Obesity is marked by metabolic inflammation and by metabolic impairment caused by increased endotoxin, free fatty acids, and vascular endothelial growth factor (VEGF) levels; and involves the endoplasmic reticulum (ER) stress as well. However, it remains unclear whether the ER stress can induce/amplify VEGF expression in metabolically-stressed monocytic cells; and if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treating cells separately with lipopolysaccharide (LPS), palmitic acid (PA), and oleic acid (OA), in presence/absence of ER stressor thapsigargin (TG). Gene expression of VEGF/ER stress markers was assessed by qRT-PCR, protein expression by ELISA, ROS by DCFH-DA assay, phosphorylation of HIF-1α, NF-κB, ERK1/2, and p38 MAPK by immunoblotting, and the insulin response in stressed cells by glucose-uptake assay. Regarding clinical analyses, adipose VEGF gene and protein expression was detected using qRT-PCR and IHC, respectively, while plasma hs-CRP, TNF-α, MDA, and OX-LDL levels were measured by ELISA. The experimental data show that a cooperative interaction between the metabolic and ER stresses led to the expression of VEGF, ROS, CHOP, ATF6, SOD2, and NRF2 (P˂0.05), as well as stimulated the CHOP and NRF2 promoter activities in reporter cells (P˂0.05). However, the glucose uptake was not impaired. The VEGF expression was dependent on phosphorylation of HIF-1α, NF-κB, and p38 MAPK; and the inhibitors of NF-κB/MAPK pathways as well as antioxidants or ROS scavengers suppressed the VEGF production. Further, individuals with obesity showed increased VEGF expression which associated positively with plasma levels of hs-CRP, TNF-α, MDA, and OX-LDL (P≤0.05). Overall, our findings support a cooperativity model in which the ER and metabolic stresses interact to augment VEGF expression in monocytic cells via the mechanisms involving CHOP/ROS/HIF-1α/NRF2 and NF-κB/p38 MAPK pathways. Disclosure S.A.K.Sindhu: None. F.Alzaid: None. F.Almulla: None. R.Ahmad: None. N.Akhter: None. A.Wilson: None. H.Arefanian: None. A.Al madhoun: None. R.S.Thomas: None. S.P.Kochumon: None. F.Alrashed: None. F.Bahman: None. Funding Kuwait Foundation for the Advancement of Sciences (RA2015-027, RA2010-003, RAHM-2019-022)

Expression of genes for transport of water and angiogenesis, as well as biochemical biomarkers in Holstein dairy cows during the ovsynch program

Changes in expression of genes associated with angiogenesis and transport of water by cells, as well as biomarkers of oxidative stress were determined at specific times during the ovsynch protocol to synchronize estrus and breed Holstein dairy cows. Blood samples were taken from 82 lactating Holstein cows at the time of the 1st GnRH injection (G1), 7 days later at the time of the PGF2a (PG) injection, and 48 h after the PGF2a treatment when the second injection of GnRH was administered (G2). The serum was analyzed for malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase (GPX), nitric oxide (NO), catalase (CAT), and total antioxidant capacity (TAC). The expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), endothelial nitric oxide synthase (eNOS3), aquaporin 3 (AQP3), and AQP4 mRNAs in peripheral blood mononuclear cells (PBMCs) was analyzed. The number of copies of each of the mRNAs was quantified using qPCR. Pregnancy status was determining at 32 ± 3 days after insemination using an ultrasound “Sonoscape-5V″ model. Receiver operating curves (ROC) were used to assess the sensitivity and specificity of the biochemical parameters in serum to predict establishment of p The expression of MDA, GPX, and Catalase changed (P < 0·05) between G1, PG and G2 phases of the ovsynch protocol with higher levels at PG than at G1 and G2. The highest levels of NO were detected at G2. The ROC analyses identified NO, TAC and CAT as the most sensitive and specific biomarker for pregnancy with areas under the curve being 0.875 (P < 0.0001), 0.843 (P < 0.03), 0.833 (P < 0.017), sensitivity being 75.3, 42.86, and 26.27%, and specificity being 90, 90 and 85% respectively. The expression for VEGF, VEGFR2, eNOS3, AQP3, and AQP4 mRNAs was upregulated at PG compared to G1 and G2 phases of the ovsynch protocol. The results suggest that following the first injection of GnRH, there is an increase in expression of VEGF, VEGFR2, eNOS3, AQP3, and AQP4 mRNAs by the time of the PGF2a injection and then expression decreased. Further, ROC analyses identified increases in NO, TAC and CAT as the most sensitive and specific biomarkers with the greatest potential to predict establishment of pregnancy in Holstein cows.

Reprogramming of VEGF-mediated extracellular matrix changes through autocrine signaling

ABSTRACT Vascular endothelial growth factor (VEGF) plays key roles in angiogenesis, vasculogenesis, and wound healing. In cancers, including triple negative breast cancer (TNBC), VEGF has been associated with increased invasion and metastasis, processes that require cancer cells to traverse through the extracellular matrix (ECM) and establish angiogenesis at distant sites. To further understand the role of VEGF in modifying the ECM, we characterized VEGF-mediated changes in the ECM of tumors derived from TNBC MDA-MB-231 cells engineered to overexpress VEGF. We established that increased VEGF expression by these cells resulted in tumors with reduced collagen 1 (Col1) fibers, fibronectin, and hyaluronan. Molecular characterization of tumors identified an increase of MMP1, uPAR, and LOX, and a decrease of MMP2, and ADAMTS1. α-SMA, a marker of cancer associated fibroblasts (CAFs), increased, and FAP-α, a marker of a subset of CAFs associated with immune suppression, decreased with VEGF overexpression. Analysis of human data from The Cancer Genome Atlas Program confirmed mRNA differences for several molecules when comparing TNBC with high and low VEGF expression. We additionally characterized enzymatic changes induced by VEGF overexpression in three different cancer cell lines that clearly identified autocrine-mediated changes, specifically uPAR, in these enzymes. Unlike the increase of Col1 fibers and fibronectin mediated by VEGF during wound healing, in the TNBC model, VEGF significantly reduced key protein components of the ECM. These results further expand our understanding of the role of VEGF in cancer progression and identify potential ECM-related targets to disrupt this progression.

Application of a Dual-Probe Coloading Nanodetection System in the Process Monitoring and Efficacy Assessment of Photodynamic Therapy: An In Vitro Study.

The oxygen-consuming property of photodynamic therapy (PDT) affects its effects and aggravates tumor hypoxia, thus upregulating the vascular endothelial growth factor (VEGF) to exacerbate tumor metastasis and lead to treatment failure. Therefore, it is necessary to monitor the dynamic changes in the factors related to PDT and tumor development trends in real time, thus helping to improve PDT efficiency. This study fabricated a fluorescent probe, TPE-2HPro, and a fluorescein-labeled aptamer probe, FAM-AptamerVEGF, to detect hydrogen peroxide (H2O2) and VEGF through the photoinduced electron-transfer effect and the specific affinity of the aptamer to VEGF, respectively. The two probes were loaded into the inner pores and absorbed on the surface of polydopamine coating-wrapped mesoporous silica nanoparticles (MSN@PDA) to construct the dual-probe-loaded system, MSNTH@PDAApt, which was kept stable in fetal bovine serum (FBS) solution and achieved pH-responsive release behavior, thus helping to increase the accumulation of the two probes in tumor cells. The dichloroacetic acid-mediated in vitro antitumor tests showed that the changing trends of H2O2 and VEGF levels were consistent with the results of related mechanism studies and could be monitored by MSNTH@PDAApt. The in vitro chlorin e6 (Ce6)-mediated PDT treatment demonstrated that when the illumination condition was 650 nm, 50 mW/cm2 for 10 min, cells were more inclined to metastasis and invasion rather than death due to a substantial increase in VEGF expression at the low Ce6 concentrations. With the increase of the Ce6 concentration, the growth of the H2O2 level gradually exceeded that of VEGF, and the reactive oxygen species (ROS)-mediated cell death dominated when the Ce6 concentration was about 2 times its IC50 values. Besides, hypoxia also affected the H2O2 and VEGF changes. These results demonstrated that MSNTH@PDAApt could precisely monitor and assess the tumor development trends during PDT treatment, thus helping improve the treatment effect.

Inverse correlation of CD3 & vascular endothelial growth factor in incisional oral squamous cell carcinoma biopsies predicts nodal metastasis & poor survival of patients.

Oral squamous cell carcinoma (OSCC) is widely prevalent in the Indian subcontinent mainly due to habit-associated aetiologies. Immune regulation and angiogenesis are the part of tumourigenesis that play a crucial role in metastasis and survival. However, the concurrent expression of vascular endothelial growth factor (VEGF) and CD3 (immune regulator receptor on T-lymphocyte) in the same OSCC tissue samples has not been reported in the Indian population. The present study evaluated the expression of CD3+ T-cells and VEGF in OSCC tissue samples and studied the clinicopathological correlation and survival analysis in an Indian population. This was a retrospective study conducted on 30 formalin-fixed and paraffin embedded sections which were histologically diagnosed as OSCC cases comprising of 15 metastatic OSCC and 15 non-metastatic OSCC with available clinical data and survival status. Reduced expression of CD3+ T-cells and increased VEGF expression were observed in metastatic OSCC samples. The correlation of expression of CD3+ T-cells and VEGF with clinicopathological parameters showed a significant association between these markers with age, nodal status, site of the lesion and survival. Reduced expression of CD3+ T-cells in OSCC was found to be associated with a significantly poor survival. VEGF was found to be over expressed in metastatic OSCC as compared to that in non-metastatic OSCC. The study findings suggest that the evaluation of CD3 and VEGF in incisional OSCC biopsies can be considered for predicting the survival outcome and metastasis.

VEGF-Expressing Mesenchymal Stem Cell Therapy for Safe and Effective Treatment of Pain in Parkinson’s Disease

Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor that mediates the differentiation and function of vascular endothelial cells. VEGF has been implicated in modulating various pains. However, the effects of VEGF in Parkinson’s disease (PD)-related pain have not been studied. The goal of this study was to understand the effects of VEGF-expressing mesenchymal stem cells (MSCs) on PD-related pain and the involved mechanisms. We used two types of MSCs: hAMSC-Vector-GFP and hAMSC-VEGF189-GFP in PD mice. Then, the expression of VEGF and the viability have been compared between two types of MSCs. To demonstrate the therapeutic effect of hAMSC-VEGF189-GFP, we transplanted each cell line in a PD mouse model. Head mechanical withdrawal thresholds were examined. hAMSC-VEGF189-GFP was associated with significantly increased VEGF expression and slightly increased viability, compared with hAMSC-Vector-GFP. The transplanted hAMSC-VEGF189-GFP significantly improved mechanical allodynia and inhibited transient receptor potential vanilloid 1 (TRPV1) expression in site. And such pain relief effects could be partially blocked by TRPV1 agonist. However, we did not observe tumor generation or neuron degeneration in hAMSC-VEGF189-GFP-transplanted animals. Taken together, our data suggest that hAMSC-VEGF189-GFP is safely therapeutically appropriate for treating PD-related pain. VEGF inhibits TRPV1 expression, which may contribute to its analgesic properties.

Correlation between Endometrial Vascular Endothelial Growth Factor Expression and Pregnancy Outcome of Frozen-Thawed Embryo Transfer in Patients with Repeated Implantation Failure.

Objective Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that is essential to numerous physiological and pathological processes. VEGF also contributes to embryo implantation by promoting embryo development, enhancing endometrial receptivity (ER), and promoting interactions between the endometrium and developing embryo. Changes in VEGF expression are linked to repeated implantation failure (RIF). Control endometrial tissues demonstrated an increase in VEGF expression during the implant window period, which promoted early villous vascularization and embryo implantation. The purpose of this study is to investigate the relationship between RIF and the expression of ER markers, such as VEGF during the implantation window stage. Methods The Yinchuan Maternal and Child Health Hospital collected 192 cases of FET endometrial tissues in the implantation window stage between January 2019 and December 2021. Immunohistochemistry was utilized to measure the levels of VEGF expression in patients with RIF (RIF group, n = 82) and patients with a successful pregnancy (control group, n = 110). The relationship between VEGF and the RIF group was analyzed using Spearman's correlation coefficient. Results VEGF levels were significantly lower during the implantation window stage (P < 0.05). Conclusion VEGF was expressed in planting window stage. The decrease of VEGF during the implantation window was correlated with RIF.

Immunosuppressive effects of vascular endothelial growth factor (Review)

Vascular endothelial growth factor (VEGF) serves a critical role in vasculogenesis, angiogenesis, tumor, inflammatory angiogenesis and lymphangiogenesis. Since 2004, bevacizumab (Avastin), a humanized anti-VEGFA monoclonal antibody, has been approved for the treatment of non-small cell lung, breast, kidney and ovarian cancer in combination with standard chemotherapy. VEGF has been demonstrated to be important in the clinic as a therapeutic target in the anti-angiogenic approach to cancer therapy. The targeting of VEGF, together with immunotherapy, has been reported to be able to reverse the immunosuppressive effects of VEGF. A positive correlation between VEGF expression and the reduced survival rates of patients with cancer has also been demonstrated. Furthermore, increased VEGF expression can lead to immune suppression via the inhibition of dendritic cell maturation, the reduction of T-cell tumor infiltration and the promotion of inhibitory cell types in the tumor microenvironment.

Effect of Li-ESWT on Testicular Tissue and Function in Androgen-Deficient Rat Model.

Low-intensity extracorporeal shockwave therapy (Li-ESWT), as a microenergy therapy, has the effects of inhibiting oxidative stress, antiapoptosis, and tissue repair, which is increasingly applied to a variety of diseases. Our research aims to explore the protective effects of Li-ESWT in the aging rat model and its possible molecular mechanism through in vivo and in vitro experiments. In vitro, TM3 Leydig cells incubated with H2O2 were treated with Li-ESWT at 4 energy levels (0.01, 0.05, 0.1, and 0.2 mJ/mm2). In vivo, we employed an androgen-deficient rat model to simulate male aging and treated it with Li-ESWT at three different energy levels (0.01, 0.05, and 0.2 mJ/mm2). Li-ESWT increased the expression of vascular endothelial growth factor (VEGF) in TM3 cells, improved antioxidant capacity, and reduced apoptosis, with the effect being most significant at 0.05 mJ/mm2 energy level. In androgen-deficient rat model, LI-ESWT can improve sperm count, motility, and serum testosterone level, enhancing tissue antioxidant capacity and antiapoptotic ability, and the effect is most significant at 0.05 mJ/mm2 energy level. Therefore, Li-ESWT at an appropriate energy level can improve sperm count, motility, and serum testosterone levels in androgen-deficient rat models, reduce oxidative stress in the testis, and increase antioxidant capacity and antiapoptotic abilities. The mechanism of this condition might be related to the increased VEGF expression in Leydig cells by Li-ESWT.

Effect of paeoniflorin on distal survival of random flaps

BackgroundDistal ischemic necrosisis a common complication of orthopedic random skin flaps surgery. Paeoniflorin, a natural compound extracted from Paeonia lactiflora, can enhances angiogenesis and alleviates excessive inflammatory response. We investigated the changes of ischemic extra-long flaps with paeoniflorin and its possible mechanism. MethodsWe raised dorsal McFarlane flaps in 54 Sprague-Dawley rats. We designed three groups of rats: high-paeoniflorin group (HP, 50 mg/kg/d), low-paeoniflorin group (LP, 20 mg/kg/d), and control group. The flap survival rate was calculated, seven days after flap construction.Blood perfusion was detected by laser Doppler flow imaging, and angiogenesis wasdetected by Lead oxide/gelatin angiography.Oxidative stress levels of flaps were determined by detecting superoxide dismutase (SOD) and malondialdehyde (MDA). The histopathological status of flap was evaluated by hematoxylin and eosin (H&E) staining.Immunohistochemistry was used to determine the expression of high mobility group protein B1 (HMGB1), nuclear factor-kappa B (NF-κB), Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, IL-18, vascular endothelial growth factor (VEGF), cysteine protease-1 (caspase-1) and NLPR3. ResultsThe flap survival rates and SOD activity in the experimental groups were significantly higher, while MDA activity was lower. Experimental groups showed significantly improved microcirculatory blood flow to the flap and increased angiogenesis. Immunohistochemistry revealed that paeoniflorin was associated with significantly increased VEGF expression, and decreased level of HMGB1, TLR4, TNF-α, NF-κB, IL-6, IL-1β, caspase-1, NLPR3, and IL-18. ConclusionsPaeoniflorin effectively enhanced the survival of rat random skin flaps by promoting vascular hyperplasia, inhibiting pyroptosis, and down-regulating inflammation.

Postnatal Exposure to Brief Hypoxia Alters Brain VEGF Expression and Capillary Density in Adult Mice.

Perinatal hypoxia leads to changes in cerebral angiogenesis and persistent structural and functional changes in the adult brain. It may also result in greater vulnerability to subsequent challenges. We investigated the effect of postnatal day 2 (P2) hypoxic preconditioning on adult brain capillary density and brain vascular endothelial growth factor (VEGF) expression in mice. P2 mice were exposed to hypoxia (5% O2) in a normobaric chamber for 2h then returned to normoxia while their littermates remained in normoxia (P2 control). After 2-6months, they were euthanised and their brains were removed for capillary density determination. Another set of animals (P2 hypoxic mice and P2 controls) were euthanised at 2, 10, 23, and 60days after birth and brain VEGF expression was assessed by western blot. Adult brain capillary density was significantly increased in the P2 hypoxic mice when compared to the P2 control mice. Additionally, VEGF expression appeared to be elevated in the P2-hypoxia mice when compared to the P2-control mice at all time points, and VEGF levels in P2-hypoxia mice declined with age similarly to P2-control mice. These data demonstrate that transient early-postnatal hypoxic stress leads to an increase in capillary density that persists in the adult, possibly due to increased VEGF expression. These results might be explained by epigenetic factors in the VEGF gene.

The Effectiveness of Local Application of Melatonin in the Original Dermal Film in Experimental Thermal Trauma

Background: The development and pathogenetic substantiation of the new agents used for local therapy of thermal trauma (TT) is an urgent problem in medicine. Melatonin (MT) is an endogenous factor of homeostasis regulation with pleiotropic potential. The aim of our study was to assess the morphology, expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), indicators of repair, oxidative destruction of lipids in the skin lesion focus in the dynamics of experimental TT under the conditions of using the original dermal film (DF) with MT. Methods and Results: The experiment was performed on 104 male Wistar rats weighing 200-240 g. For modeling TT II degree according to ICD-10 a relative area of 3.5% of the body surface, an interscapular region isolated from the surrounding tissues, was immersed in distilled water at 98-99 °C for 12 sec. DF based on sodium carboxymethylcellulose with an area of 12 cm2 with MT at a concentration of 5 mg/g was applied daily for five days. The wound area and epithelialization rate were calculated. The content of MMP-9 and VEGF in the burn wound was assessed by an immunohistochemical method. In the homogenate of the burn wound, the content of LPO products was assessed. Morphological and biochemical studies were performed on Days 5, 10 and 20 after TT induction. With experimental TT from Day 5 to Day 20, the absolute area of the burn wound decreases by 35%, the rate of epithelialization increases, the number of neutrophils in the focus of thermal damage decreases, while the representation of lymphocytes, histiocytes, and fibroblasts increases; the expression of MMP-9 and VEGF increases; predominantly secondary and final LPO products in the heptane phase accumulate, the final products of LPO in the isopropanol phase of the lipid extract. The use of MT in the composition of DF daily for 5 days with experimental TT leads to a decrease in the area of the wound defect (by 46% of the original area on Day 20), an increase in the rate of its epithelialization, an increase in the content of lymphocytes and fibroblasts in the burn wound on Days 5, 10 and 20 of TT, a decrease in the representation of neutrophils and macrophages on Days 5 and 10, as well as an increase in VEGF expression on Days 5 and 10, MMP-9 - on Day 5 and a decrease in MMP-9 expression on Days 10 and 20 of TT. In addition, the use of MT in the composition of DF leads to a decrease in the content of predominantly secondary and end products of LPO in the heptane and isopropanol phases of the burn wound on Days 10 and 20 of TT. Correlation analysis revealed that a decrease in the burn surface area under a local application of MT occurs with an increase in the content of VEGF in the wound area and a decrease in the content of MMP-9 and secondary and final LPO products in the heptane phase and the isopropanol phase. On Day 20, there were direct moderate correlations between the absolute burn surface area, on one hand, and secondary and final LPO products, on the other, in the heptane phase (R=0.51, R=0,68; P&lt;0.05) and the isopropanol phase (R=0.44, R=0.46; P&lt;0.05), respectively. Conclusion: The results obtained expand the existing understanding of the role of changes in the expression of MMP-9 and VEGF in the pathogenesis of TT. We believe that the repair-stimulating effect of MT in the DF, which we established during TT at the preclinical stage, is associated with the LPO-limiting effect of MT and a change in the expression of MMP-9 and VEGF in the burn wound and is a prerequisite for further study of the mechanism of action and the effectiveness of MT application in clinical conditions in TT.