Vascular Endothelial Growth factor-A Levels Research Articles

ALKBH5 knockdown suppresses gastric cancer progression by reducing the expression of long non-coding RNA TUG1.

This study aimed to explore the relationship between m6A demethylase ALKBH5 and long noncoding RNA TUG1 (TUG1), as well as their effects on proliferation, migration, and angiogenesis in gastric cancer (GC) cells. The Cancer Genome Atlas (TCGA) database was utilized to analyze the relative expression levels of ALKBH5, TUG1, and vascular endothelial growth factor A (VEGFA). Survival analyses of TUG1, ALKBH5, and VEGFA were performed using the Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier databases. The binding sites of TUG1 and ALKBH5 were predicted using the Annolnc2 database. The correlation between ALKBH5 and TUG1 expression was analyzed using the GEPIA database. Subsequently, small interfering RNA (siRNA) targeting ALKBH5 and TUG1 was transfected into SGC-7901 cells, and functional studies were conducted using quantitative real-time polymerase chain reaction (qRT-PCR), CCK-8 assays, colony formation assays, transwell assays, and angiogenesis assays. Bioinformatics analysis indicated that ALKBH5, TUG1, and VEGFA were highly expressed in gastric cancer tissues and exhibited a positive correlation. Survival analysis revealed that high expression levels of ALKBH5, TUG1, and VEGFA were significantly associated with poor prognosis in gastric cancer patients. Binding sites for TUG1 and ALKBH5 were identified. Functional experiments demonstrated that the knockdown of ALKBH5 resulted in the downregulation of TUG1, which subsequently reduced the proliferation, invasion, migration, and angiogenesis of gastric cancer cells. The m6A demethylase ALKBH5 promotes gastric cancer progression by erasing the methylation modification of TUG1 and increasing TUG1 expression. This finding provides a new perspective for the treatment and prognosis assessment of gastric cancer.

Effects of atropine on choroidal hemodynamics and VEGFA and HIF-1α expression in form-deprivation myopia guinea pigs.

We investigated the mechanism of action of atropine in myopia control by examining its effect on choroidal hemodynamics. Blood flow was evaluated using indocyanine green (ICG) fluorescence and molecular variation during the development of form-deprivation myopia (FDM) and atropine treatment in guinea pigs. Guinea pigs were divided randomly into the normal control (NC), FDM, and FDM+1% atropine (ATR) groups, and evaluated by spherical equivalent refractive error (SE) and axial length (AL). Choroidal hemodynamic parameters were measured via ICG fluorescence imaging including the maximal ICG fluorescence intensity (Imax), rising time (Trising), blood flow index (BFI), and mean transit time (MTT). Additionally, the expression in the choroid-RPE complex of choroidal vascular endothelial growth factor A (VEGFA) and HIF-1 α were assessed via Western blotting. Atropine inhibited the development of FDM, with effects of FD on both SE and AL being reduced. ICG fluorescence hemodynamic wide-field maps and time-series curves revealed that the atropine significantly accelerated choroidal blood flow, with reduced Trising and MTT, while increasing Imax, BFI and the number of lobulated choriocapillaris structures compared with the FDM group. In terms of molecular markers, atropine inhibited the effect of FDM, increasing VEGFA levels and reducing HIF-1α expression. These findings suggest that atropine improved choroidal hemodynamics and changed vascular markers, potentially contributing to its role in inhibiting the progression of myopia in the FDM model.

Potential of Trilayered Gelatin/Polycaprolactone Nanofibers for Periodontal Regeneration: An In Vitro Study.

Over the past few years, biomaterial-based periodontal tissue engineering has gained popularity. An ideal biomaterial for treating periodontal defects is expected to stimulate periodontal-derived cells, allowing them to contribute most efficiently to tissue reconstruction. The present study focuses on evaluating the in vitro behavior of human periodontal ligament-derived stromal cells (hPDL-MSCs) when cultured on gelatin/Polycaprolactone prototype (GPP) and volume-stable collagen matrix (VSCM). Cells were cultured onto the GPP, VSCM, or tissue culture plate (TCP) for 3, 7, and 14 days. Cell morphology, adhesion, proliferation/viability, the gene expression of Collagen type I, alpha1 (COL1A1), Vascular endothelial growth factor A (VEGF-A), Periostin (POSTN), Cementum protein 1 (CEMP1), Cementum attachment protein (CAP), Interleukin 8 (IL-8) and Osteocalcin (OCN), and the levels of VEGF-A and IL-8 proteins were investigated. hPDL-MSCs attached to both biomaterials exhibited a different morphology compared to TCP. GPP exhibited stronger capabilities in enhancing cell viability and metabolic activity compared to VSCM. In most cases, the expression of all investigated genes, except POSTN, was stimulated by both materials, with GPP having a superior effect on COL1A1 and VEGF-A, and VSCM on OCN. The IL-8 protein production was slightly higher in cells grown on VSCM. GPP also exhibited the ability to absorb VEGF-A protein. The gene expression of POSTN was promoted by GPP and slightly suppressed by VSCM. In summary, our findings indicate that GPP electrospun nanofibers effectively promote the functional performance of PDLSCs in periodontal regeneration, particularly in the periodontal ligament and cementum compartment.

Eugenol inhibits NEAT1 as a ceRNA in pre-cancerous breast lesions.

Eugenol (EU) from cloves is highly effective against different tumors. The long noncoding ribonucleic acids (lncRNAs), which play a role of competing endogenous RNAs (ceRNAs), suppress microRNAs (miRNAs) involved in post-transcriptional regulatory networks. The present work focused on analyzing how EU affected pre-cancerous breast lesions (PBL). Initially, the gene expression profiles of patients (n=880) in the National Center for Biotechnology Information (NCBI) database were analyzed. Further, we established a lncRNA-miRNA-mRNA ceRNA network through bioinformatics analysis and investigated mechanistic roles of lncRNAs as ceRNAs and the anti-tumor effect of EU using MCF-10AT cells in vitro as well as PBL model rats in vivo. Besides, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), miR-383-5p, miR-9-5p, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A) expression was examined through quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemical staining analyses. There were altogether 1162 mRNAs, 81 miRNAs, and 26 lncRNAs recognized as trend genes in breast cancer (BC) and pre-cancerous BC (pBC), constructing the ceRNA network using 3 lncRNAs, 3 miRNAs, and 38 mRNAs. It was observed that NEAT1, miR-383-5p, miR-9-5p, VEGF-A, and MMP-9 were downregulated in breast tumor cells in accordance with bioinformatics analysis. EU suppressed MCF-10AT cell growth, decreasing the NEAT1, VEGF-A, and MMP-9 levels and increasing miR-383-5p and miR-9-5p expressions in vitro and in vivo. In summary, the EU reduced the VEGF-A and MMP-9 expressions via NEAT1-mediated miR-383-5p and miR-9-5p against PBL, indicating that the EU may be a promising external drug to act against PBL.

Development and nomogram prediction of early postoperative recurrence in hepatocellular carcinoma based on preoperative CT imaging radiomic features and serum features related to microvascular infiltration.

Hepatocellular carcinoma (HCC) is characterized by high postoperative recurrence rates, and predicting early recurrence is crucial for improving clinical outcomes, yet remains challenging. Both preoperative computed tomography (CT) imaging radiomic features and serum biomarkers related to microvascular infiltration are important indicators of HCC prognosis. This study aimed to develop a nomogram model incorporating both preoperative CT radiomic features and serum biomarkers associated with microvascular infiltration to predict early postoperative recurrence in HCC patients. The study included 156 HCC patients who underwent radical surgery at the Tumor Hospital Affiliated to Nantong University between January 2021 and January 2022. Preoperative CT imaging data were obtained for each patient, and radiomic features were extracted using the 3D Slicer software. Preoperative serum biomarkers related to microvascular invasion were collected, including alpha-fetoprotein (AFP), vascular endothelial growth factor A (VEGF-A), Speckled Protein 100 (SP100), and the Fibrosis-4 (FIB-4) index levels. Postoperative follow-up was conducted for 2 years, during which recurrence data were collected. The radiomics score was generated through dimensionality reduction and least absolute shrinkage and selection operator (LASSO) regression analysis. Univariate and logistic regression analyses were used to identify independent risk factors for early postoperative recurrence of HCC. The nomogram model was constructed using R language, and its predictive performance was evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis curves. Among the 156 patients, 60 experienced early recurrence, while 96 did not. Feature reduction through LASSO regression identified 10 optimal features from the venous phase and 4 optimal features from the arterial phase, leading to the development of a radiomics score formula. The early recurrence group had significantly higher radiomics scores than the non-early recurrence group [-1.35 (-2.29, 1.21) vs. 0.94 (-0.40, 1.87), P<0.001]. Logistic multivariate regression analysis identified lesion number, Edmondson grade, AFP and VEGF-A levels, and radiomics score as independent risk factors for early postoperative recurrence of HCC (P<0.05). The nomogram model demonstrated high predictive performance with area under the curve (AUC) values of 0.9265 and 0.9255 in the training and internal test sets, respectively. The model demonstrated good net benefit across a threshold range of 0.01-75%, effectively identifying high-risk patients for early postoperative recurrence. The nomogram model based on preoperative serum biomarkers related to microvascular infiltration and CT radiomic features demonstrated high predictive performance for early postoperative recurrence of HCC. However, further studies, including external validation, are needed to establish the model's generalizability and clinical applicability.

Progress and perspectives on BMP9-ID1 activation of HIF-1α and VEGFA to promote angiogenesis in hepatic alveolar echinococcosis.

Hepatic alveolar echinococcosis is a zoonotic disease with a high incidence in western China, particularly affecting plateau areas such as Qinghai, Tibet, and Xinjiang. Research has indicated the presence of neovascularization in the peripheral infiltration area of hepatic alveolar echinococcosis, with a strong correlation between angiogenesis and vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1-alpha (HIF-1α) overexpression. Given the similarities between hepatic alveolar echinococcosis and liver cancer, current research is focused on treating the disease by targeting related signaling pathways using molecular drugs used for liver cancer. This article aims to summarize the biological regulation of HIF-1α and VEGFA overexpression in angiogenesis related to hepatic alveolar echinococcosis, as well as the impact of the BMP9-ID1 signaling pathway on the expression levels of HIF-1α and VEGFA, providing new insights for potential treatment strategies.

Agrimoniae Herba-Coptidis Rhizoma inhibits angiogenesis in colorectal cancer inflammatory microenvironment based on network pharmacology and experiment validation

This study aims to investigate the effect and mechanism of the herb pair Agrimoniae Herba-Coptidis Rhizoma in inhibiting angiogenesis in the colorectal cancer inflammatory microenvironment by using the method of network pharmacology and the zebrafish model. The method of network pharmacology was employed to obtain the active components, potential core targets, and signaling pathways regulated by the herb pair in inhibiting angiogenesis in the inflammatory microenvironment of colorectal cancer, on the basis of which the underlying mechanism was predicted. The zebrafish model of colorectal cancer was established, and the inflammatory microenvironment was modeled. The effects of different concentrations of the herb pair on the area, number, and length of intersegmental vessels(ISVs) of the zebrafish model were observed. Western blot and real-time quantitative PCR were employed to measure the protein and mRNA levels, respectively, of vascular endothelial growth factor A(VEGFA), vascular epidermal growth factor receptor 2(VEGFR2, also known as kdrl, Flk1), and vascular epidermal growth factor receptor 3(VEGFR3, also known as Flt4). A total of 18 active components and 488 potential targets of Agrimoniae Herba-Coptidis Rhizoma were predicted, and 108 common targets were shared by the herb pair and the disease. According to the results of KEGG pathway enrichment analysis, the angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway were selected for verification. The zebrafish experiment showed that compared with the blank group, the model group showed increased area, number, and length of ISVs in the inflammatory microenvironment. Compared with the model group, the herb pair decreased the area, number, and length of ISVs in a concentration-dependent manner. Compared with the blank group, the model group showed up-regulated protein and mRNA levels of VEGFA, kdrl, and Flt4 in the inflammatory microenvironment. Compared with the model group, the herb pair down-regulated the protein and mRNA levels of VEGFA, kdrl, and Flt4 in a concentration-dependent manner. The results indicated that in the colorectal cancer inflammatory microenvironment, the herb pair Agrimoniae Herba-Coptidis Rhizoma could inhibit angiogenesis via multiple components, targets, and pathways. The anti-angiogenesis effect might be related to the down-regulation of the expression levels of angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway.

Bioinformatics Combined With Experimental Modeling to Study the Molecular Mechanism of Xuefu Zhuyu Decoction to Improve Erectile Dysfunction Associated With Asthma in Rats.

Asthma is associated with chronic systemic inflammation, and inflammatory factors can damage vascular endothelial cells, thus impairing erectile function (ED). Xuefu Zhuyu decoction (XFZYD) can inhibit inflammation and promote angiogenesis, which in turn improves asthma as well as ED, but its exact mechanism of action is not yet clear. This study investigates the mechanism underlying the beneficial effect of XFZYD on asthma-associated ED. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze the constituents of XFZYD, and network pharmacology analysis was used to predict the target genes of XFZYD. Sprague-Dawley rats in the asthma model with erectile dysfunction were divided into the model, XFZYD low-, medium-, and high-dose group (3.09, 6.17, and 12.34 g/kg), with drug intervention for 8 weeks. We assessed the interleukin 6 (IL-6), vascular endothelial growth factor A (VEGFA), and tumor necrosis factor (TNF) protein levels in the penile tissue. We discovered that after treatment with XFZYD (3.09, 6.17, and 12.34 g/kg), the number of erections significantly increased (1.17 ± 0.41, 1.50 ± 0.55, and 1.67 ± 0.52), the density of endothelial cells in the corpus cavernosum of the penis increased, the expression level of IL-6 was reduced (7.5%, 21.2%, and 24.4%), the expression level of VEGFA was reduced (7.8%, 25%, and 28.4%), and the expression level of TNF was reduced (13.5%, 30.6%, and 32.4%). The in vivo experiments indicate that XFZYD may improve ED in asthma model rats by inhibiting inflammation and reducing vascular permeability. This study provides new insights into the mechanism of action of XFZYD in the treatment of asthma leading to ED.

Assessing Vascular Biomarkers and Their Association with Hypertension in Paediatric Chronic Kidney Disease

Objectives: This study aims to examine the correlation between children with chronic kidney disease (CKD) and endothelial dysfunction biomarkers, including asymmetric dimethylarginine (ADMA), angiopoietin-2 (Ang-2), and vascular endothelial growth factor-A (VEGF-A), as well as blood pressure and cardiovascular risk. Methods: A cross-sectional study included 90 children divided into two groups: 45 with CKD with different stages and 45 healthy controls. Blood pressure was taken, and levels of ADMA, Ang-2, and VEGF-A were determined. November 2021 to October 2022 was the time frame of the study. Results: The results showed that children with CKD had significantly higher levels of ADMA, Ang-2, and VEFG-A compared to the control group. Systolic and diastolic blood pressure showed a positive connection with the elevated biomarkers but estimated glomerular filtration rate (eGFR) showed a negative association. Conclusion: Increased cardiovascular risk and antihypertensive have been associated with elevated levels of VEFG-A, Angiopoietin-2, and ADMA in children with chronic kidney disease. These biomarkers might be useful in clinical evaluations to improve therapy and results for children with CKD.

Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma

Stereotactic body radiation therapy (SBRT) has evolved as a treatment alternative for advanced hepatocellular carcinoma (HCC) patients who are ineligible for other local therapies. Posttreatment responses are assessed by imaging modalities, serum AFP, and protein induced by vitamin K absence-II (PIVKA) II levels. Despite good specificity, both AFP and PIVKA-II have low to medium sensitivity. The study aimed to find more effective biomarkers that have an impact on the survival outcomes of the patients. We have prospectively collected blood samples from 18 patients undergoing SBRT. Serum levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A) were analyzed kinetically pre-SBRT following day 5 and day 30 post-SBRT. Local control (LC), overall survival (OS), progression free survival (PFS), and postprocedure adverse events were recorded. The cohort had a median follow-up duration of 12.5 months (range 4-30 months). In the entire cohort, the estimated mean OS was 21.2 months (95% confidence interval [CI], 15.9-26.4), and the median progression free survival (mPFS) was 8 months (95% CI, 1.7-14.2). Patients with higher PIVKA-II levels (pre- and post-SBRT) also showed increased concentrations of VEGF-A and HGF. Patients with metastasis at presentation had higher HGF (P=0.028) and VEGF-A (P=0.027) concentrations compared to the nonmetastatic group. Patients with increased levels of VEGF-A and HGF at day 30 post-SBRT compared to day 5 had poor PFS. Indeed, the mPFS was 22 months vs 6 months (P=0.301) in patients with low VEGF-A post SBRT on day 30 compared to day 5. Similarly, mPFS in patients with increase in HGF was 6 months as compared to 22 months (P=0.326) in patients in whom HGF was reduced post-SBRT. We conclude that in addition to PIVKA-II, HGF, and VEGF-A can be used as prognostic and predictive markers for early progression of disease post-SBRT. However, further prospective trials are warranted in the future to validate the results.

Effects of propranolol on the biological behavior of human umbilical vein endothelial cells and the expression of SOX18, MMP-7, and VEGFA

To investigate the effects of propranolol on the proliferation, apoptosis, migration, and tube formation ability of human umbilical vein endothelial cells (HUVEC), as well as its impact on the expression of sex-determining region Y-box 18 (SOX18), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor A (VEGFA). HUVEC were treated with different concentrations of propranolol, and cell viability was assessed using the CCK-8 method to determine the optimal concentration and treatment duration. The experiment consisted of a control group and groups treated with different concentrations of propranolol (50, 100, 150 μmol/L). Apoptosis, migration, and tube formation of HUVEC were observed using flow cytometry, wound healing assays, and tube formation assays. Western blot and real-time quantitative PCR were used to detect the expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA. Compared to the control group, the apoptosis rate in the propranolol treatment groups increased significantly (P<0.05), and it rose significantly with increasing drug concentration (P<0.05). The wound healing rate decreased in the propranolol treatment groups, and both the number of tube formation nodes and total tube length were reduced (P<0.05). The expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA were downregulated in the propranolol treatment groups (P<0.05). Propranolol can inhibit the proliferation, migration, and tube formation ability of HUVEC and promote cell apoptosis, resulting in decreased expression levels of SOX18, MMP-7, and VEGFA.

Expression Profiles of Integrin-Linked Kinase, Vascular Endothelial Growth Factor A, and Ephrin Type-A Receptor 2 in Colorectal Cancer Lymph Nodes.

Background Colorectal cancer (CRC) is the third most frequently diagnosed cancer globally, with a high incidence of morbidity and mortality. Early diagnosis of CRC is crucial for determining appropriate treatment regimens, thereby prolonging overall survival rates and improving prognostic outcomes. Objectives This study aimed to investigate the expression profiles of specific proteins in the lymph nodes (LNs) of CRC patients, including integrin-linked kinase (ILK), vascular endothelial growth factor A (VEGFA), and ephrin type-A receptor 2 (EphA2), through immunohistochemical studies. Methods The study involved a sample of 76 patients clinically diagnosed with CRC who were referred by their specialist oncologist. Tumor staging was determined based on the TNM classification. Immunohistochemical studies were conducted to measure the expression patterns of the candidate markers (ILK, EphA2, and VEGFA). Expression levels were scored as negative, low, or high. Results The highest percentage of CRC patients were diagnosed with conventional adenocarcinoma, predominantly in stages II and III. Of the 76 CRC tissue specimens, the majority (46, 60.52%) tested negative for lymphatic invasion, while the remaining 30 (39.47%) tested positive. According to the TNM classification, 14 samples had N1 (one invaded LN), and 16 had N2 (two or more invaded LNs). Furthermore, the percentage of patients with low and high EphA2 expression was significantly higher (p<0.0001) compared to the negative expression controls. Regarding ILK, 15 cases (50.0%) showed negative expression, while an equal number displayed positive expression. Additionally, the group with low VEGFA expression was statistically significantly higher (p=0.01) compared to the negative control. Conclusion The expression levels of EphA2, ILK, and VEGFA were found to be higher in LNs with lymphatic invasion compared to those with negative expression, highlighting the role of these proteins in CRC progression.

Exploring the Relationship Between YAP (Yes-Associated Protein) and VEGF-A with Distant Metastasis in Nasopharyngeal Carcinoma.

To investigate the relationship between Yes-Associated Protein (YAP) and Vascular Endothelial Growth Factor-A (VEGF-A) in nasopharyngeal carcinoma (NPC) and evaluate their potential as predictive biomarkers for distant metastasis. This observational analytic study was conducted from May to August 2023, including 60 NPC cases diagnosed histopathologically at the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital. The study involved 30 NPC cases with distant metastasis and 30 without distant metastasis. Immunohistochemical analysis was performed using primary antibodies (rabbit YAP, D8H1X; mouse VEGF, clone C-1 sc-7269). Expression levels of YAP and VEGF-A were semi-quantitatively assessed using the H-score formula on 500 tumor cells. Cutoff points for YAP and VEGF-A were determined through Receiver Operating Characteristic (ROC) curve analysis and the Youden index. Statistical analyses, including Chi-square tests, were conducted using SPSS 25.0 to evaluate the relationship between marker expression and the presence of distant metastasis. A significant difference in YAP expression was observed between NPC cases with distant metastasis (80%) and those without (23.3%, p<0.001). Similarly, VEGF-A expression was notably higher in cases with distant metastasis (86.7%) compared to those without (20%, p<0.001). A significant association between YAP and VEGF-A expression was found (p=0.001). ROC curve analysis showed that YAP (AUC=0.738, 95% CI 0.602-0.874) and VEGF-A (AUC=0.842, 95% CI 0.735-0.950) effectively predict distant metastasis. The double co-high-expression group (elevated YAP and VEGF-A) exhibited a significantly higher rate of distant metastasis compared to the non-double co-high-expression group (p<0.001). Elevated expressions of YAP and VEGF-A are significantly associated with distant metastasis in NPC, suggesting their potential as biomarkers for predicting metastatic risk.

Mechanism of Qijia Rougan Decoction and its disassembled formulas on regulation of VEGF/SRF/c-FOS pathway and improvement of hepatic sinusoidal capillaryization in rats with hepatic fibrosis

This study aims to reveal the mechanism of Qijia Rougan Decoction(QJRG) and its disassembled formulas in mitigating hepatic fibrosis via the vascular endothelial growth factor(VEGF)/serum response factor(SRF)/c-FOS pathway and hepatic sinusoidal capillarization. Male Sprague-Dawley(SD) rats were randomized into a control group(n=6) and a modeling group(n=28). Hepatic fibrosis was induced by subcutaneous injection of 40% carbon tetrachloride(CCl_4) in olive oil. The successfully modeled rats were grouped as follows: model(n=7), QJRGF(n=6), disassembled formula for benefiting Qi and nourishing blood(YQYX, n=6), and disassembled formula for resolving stasis and dredging collaterals(HYTL, n=6). The rats in the YQYX, HYTL, and QJRG groups were administrated with corresponding medicines by gavage, while those in the control group and the model group were treated by gavage of normal saline. After 28 days, the rats were sacrificed, and serum and liver samples were collected. Hematoxylin-eosin staining and Masson staining were employed to observe inflammation and fibrosis, respectively, in the liver tissue. The serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured to assess the liver function. The expression levels of α-smooth muscle actin(α-SMA) and collagen Ⅰ in the liver tissue were measured to evaluate the activation of hepatic stellate cells(HSCs). The expression levels of vascular endothelial growth factor A(VEGFA), vascular endothelial growth factor receptor 2(VEGFR-2), SRF, c-FOS, cluster of differentiation 31(CD31), and von willebrand factor(vWF) in the liver tissue were measured. Scanning electron microscopy(SEM) was employed to observe the morphology of the fenestrae in liver sinusoidal endothelial cells(LSECs) to elucidate the mechanisms underlying the antifibrotic effects of QJRG and its disassembled formulas. Compared with the model group, QJRG, YQYX, and HYTL mitigated the pathological changes in the liver tissue, reduced the ALT and AST levels and liver index(P&lt;0.01), and lowered the α-SMA and collagen Ⅰ levels in the liver tissue(P&lt;0.01). QJRG, YQYX, and HYTL were capable of maintaining the fenestrae morphology of LSECs and down-regulating the protein and mRNA levels of CD31 and vWF in the liver tissue(P&lt;0.05). Moreover, they down-regulated the protein and mRNA levels of VEGFA, SRF, and c-FOS(P&lt;0.05) and restored the protein and mRNA level of VEGFR-2(P&lt;0.05). QJRG outperformed its disassembled formulas(P&lt;0.05). In summary, QJRG and its disassembled formulas can restore the liver function, mitigate pathological damage, inhibit the activation of HSCs, and alleviate hepatic fibrosis and sinusoidal capillarization by regulating the VEGF/SRF/c-FOS signaling pathway. QJRG outperforms HYTL, which suggests that the combination of nourishing and dredging has positive significance in the treatment of hepatic fibrosis and sinusoidal capillarization.

Does placental VEGF-A protein expression predict early neurological outcome of neonates from FGR complicated pregnancies?

Fetal hypoxia due to placental dysfunction is thehallmark of fetal growth restriction (FGR). Preferential perfusion of the brain (brain-sparing effect), as a part of physiological placental cardiovascular compensatory mechanisms to hypoxia, in FGR was reported. Therefore, the correlation between vascular endothelial growth factor A (VEGF-A) protein expression in the FGR placentas and newborns' early neurological outcome was examined. This study included 50 women with FGR complicated pregnancies and 30 uneventful pregnancies. Fetal hemodynamic parameters, neonatal acid-base status after delivery, placental pathohistology and VEGF-A expression were followed. Early neonatal morphological brain evaluation by ultrasound and functional evaluation of neurological status by Amiel- Tison Neurological Assessment at Term (ATNAT) were performed. VEGF-A protein expression level was significantly higher in the FGR placentas than normal term placentas (Fisher-Freeman-Halton's test, p≤0.001). No statistically significant correlation between placental VEGF-A expression and different prenatal and postnatal parameters was noticed. Whereas the alteration of an early neurological status assessed by ATNAT was found in 58 % of FGR newborns, morphological brain changes evaluated by UZV was noticed in 48 % of cases. No association between the level of placental VEGF-A expression and the early neurological deficits was found. As far as we know this is the first study of a possible connection between VEGF-A protein expression in the FGR placentas and neonates' early neurological outcomes. The lack of correlation between the FGR placental VEGF-A expression and neonates' neurological outcome could indicate that optimal early neurodevelopment may take place due to compensatory mechanism not related to placental VEGF-A expression.

Anlotinib reverses osimertinib resistance via inhibiting epithelial-to-mesenchymal transition and angiogenesis in non-small cell lung cancer.

In the present, we aimed to investigate the effect of anlotinib on the potential reversal of osimertinib resistance by inhibiting the formation of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In a clinical case, anlotinib reversed osimertinib resistance in Non-small cell lung cancer (NSCLC). We performed an immunohistochemical experiment on tumor tissues from three non-small cell lung cancer patients exhibiting osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A (VEGFA) before and after osimertinib resistance. The results revealed the downregulation of E-cadherin, coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance, compared with the expression in tissues of patients before taking osimertinib. Subsequently, we established osimertinib-resistant cell lines and found that the osimertinib-resistant cells acquired the EMT features. Then, we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT. The expression levels of VEGFA and micro-vessels were analyzed in the combination group in vitro. Finally, we explored the reversal of osimertinib resistance in combination with anlotinib in vivo with 20 nude mice. The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of resistant cells, which also inhibited tumor growth, exerted anti-tumor activity, and ultimately reversed osimertinib resistance in mice. The co-administration of osimertinib and anlotinib demonstrated their synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients, ultimately reversing osimertinib resistance.

Prospective Cytokine Profiling in Aqueous Humor Reveals a Proinflammatory Microenvironment in Highly Dense Nuclear Cataracts.

To investigate if the cytokine profile in the aqueous humor (AH) of cataract patients varies according to cataract type and severity. This prospective study included 397 eyes of 397 patients (median age, 76 years; range, 30-94 years) who underwent standard small-incision phacoemulsification surgery. Cataracts were graded using the LOCS III system: mild (≤3), moderate (3.5-5), and severe (≥5). Biometric measurements from the IOL master 700 (Zeiss, Oberkochen, Germany) were used to differentiate between thick (>4.5 mm) and thin lenses. Information about age, gender, and self-reported diseases was obtained from patient records. Eleven different proteins were measured in AH using a multiplex cytokine assay (AYOXXA Biosystems, Cologne, Germany), including IL- 6, IL-8, angiopoietin 2, C-reactive protein (CRP), vascular endothelial growth factor A (VEGF-A), platelet-derived growth factor BB, placental growth factor, CXCL12, CXCL13, and CXCL10. Statistical analysis was performed using R and included nonparametrical testing, linear regression, and k-means clustering. Higher nuclear LOCS grades correlated with increased levels of CCL2 (360 vs. 387 vs. 517 pg/mL, P < 0.001), VEGF-A (270 vs. 292 vs. 390 pg/mL, P = 0.012), IL-8 (3.1 vs. 4.2 vs. 5.7 pg/mL, P = 0.018), and CXCL10 (52 vs. 61 vs. 90 pg/mL, P = 0.003). No associations were observed for cortical and subcapsular cataracts. Thicker lenses were associated with significantly increased levels of CRP, CXCL10, CXCL12, IL-6, IL-8, and VEGF-A. The cytokine profile of AH varies based on cataract grading and lens thickness. In highly dense nuclear cataracts, CCL2, VEGF-A, IL-8, and CXCL10 were elevated.

Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR

BackgroundOral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC.MethodsThe study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC.ResultsThe results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023).ConclusionThis study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.

Chromosomal instability is associated with prognosis and efficacy of bevacizumab after resection of colorectal cancer liver metastasis

Introduction Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab. Methods Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method and Cox regression models. Results Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001–3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150–5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078–6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173–12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043). Conclusions Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6–VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

Silencing ANLN hinders the proliferation, migration, invasion, and angiogenesis of oral squamous cell carcinoma

BackgroundThe actin-binding protein anillin (ANLN) functions as an oncogene in various cancers but has not been fully studied in oral squamous cell carcinoma (OSCC). This study aimed to investigate the expression of ANLN in OSCC tissues and cell lines, to better understand its role in mediating proliferative, angiogenic, invasive, and metastatic capabilities in this type of cancer. MethodsANLN mRNA and protein levels were assessed using qPCR and western immunoblotting. The expression intensity of ANLN was evaluated using immunohistochemical (IHC) staining. Biological functional assays were employed to characterize the behavior of OSCC cells influenced by ANLN. Additionally, comprehensive bioinformatics analysis, including GO analysis and KEGG enrichment analysis, was performed on differentially expressed genes in ANLN-mediated pathways. ResultsOSCC tumors and cell lines exhibited higher ANLN expression. Silencing of ANLN significantly suppressed OSCC cell proliferation, as evidenced by a significant reduction in the Ki-67 index both in vitro and in vivo. The migration and invasive ability of OSCC cells were markedly diminished, coinciding with a decrease in epithelial-mesenchymal transition activity. ANLN was also found to promote angiogenic activity in OSCC cells, partly through synergistic effects mediated by vascular endothelial growth factor A (VEGFA). Downregulation of ANLN expression led to decreased VEGFA levels, resulting in reduced angiogenesis characterized by fewer vascular branches. ConclusionsOur findings highlight the promising role of ANLN as a biomarker for both diagnostic and prognostic in OSCC. Targeting ANLN with inhibitory strategies could impede the oncogenesis processes at the core of OSCC development, presenting significant opportunities for advancing therapeutic interventions.