Serum Vascular Endothelial Growth Factor Levels Research Articles

Relationship between serum HIF-1α and VEGF levels and prognosis in patients with acute cerebral infarction combined with cerebral-cardiac syndrome.

This research was conducted to discuss the recent prognosis of patients with acute cerebral infarction (ACI) combined with cerebral-cardiac syndrome (CCS). Eighty-seven patients with ACI were selected, which were divided into the ACI group (52 patients) and the CCS group (35 patients) according to whether the CCS was combined, and another 30 health controls were selected as the control group. Serum hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) levels of subjects in each group at the 1st day, the 3rd day, and the 7th day after admission were measured by enzyme-linked immunosorbent assay. After discharge for 30 days, the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) score were utilized to evaluate the prognosis of patients. The role of serum HIF-1α and VEGF levels in the prognosis of ACI combined with CCS patients was assessed by receiver operating characteristic curve and the binary logistic regression analysis. Higher serum HIF-1α and VEGF levels were observed in the CCS and ACI groups versus the control group, and the levels of which were even higher in the CCS group in comparison to the ACI group. According to the prognosis of the NIHSS score, fasting blood glucose (FBG), Acute Physiology and Chronic Health Evaluation II score, creatine kinase-MB (CK-MB), and HIF-1α and VEGF levels at the 7th day of admission were higher while Glasgow coma scale (GCS) score was lower in the poor prognosis group than those in the good prognosis group, and the area under the curve (AUC) of serum HIF-1α and VEGF levels was 0.895 (95% confident interval [CI], 0.786-1.000), and 0.855 (95% CI, 0.731-0.980). According to the prognosis of the mRS score, FBG, CK-MB, and HIF-1α and VEGF levels at the 7th day of admission were higher while GCS score was lower in the poor prognosis group than those in the good prognosis group, and the AUC of serum HIF-1α and VEGF levels was 0.850 (95% CI, 0.722-0.979) and 0.901 (95% CI, 0.798-1.000). The results of the binary logistic regression analysis revealed that HIF-1α and VEGF levels may be independent risk factors influencing the prognosis of ACI combined with CCS. Serum HIF-1α and VEGF have a good predictive value for assessing the recent prognosis of patients with ACI combined with CCS, which could be independent risk factors influencing the prognosis of disease.

Serum levels of SOCS6 are decreased in diabetic retinopathy and are related to severity of the disease.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM). A recent in vitro study found that the suppressor of cytokine signaling 6 (SOCS6) plays a protective role in DR and DM. However, to date, no clinical studies have focused on the role of SOSC6 in DR development. The present study aimed to investigate the expression and clinical significance of serum SOCS6 in DR. A total of 159 DR patients were enrolled in the study. Additionally, 156 type 2 DM (T2DM) patients without DR were recruited as controls. Serum levels of SOCS6, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF), and angiopoietin-2 (ANG-2) were measured using enzyme-linked immunosorbent assay (ELISA). Demographic and clinical data were collected. Age, the course of DM, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were significantly higher in proliferative DR (PDR) patients. Serum SOCS6 levels in PDR patients were remarkably lower than in non-PDR patients or non-DR T2DM patients. The Pearson's analysis showed that SOCS6 was negatively correlated with CRP, IL-6, TNF-α, IL-1β, VEGF, and ANG-2. The serum levels of CRP, IL-6, TNF-α, IL-1β, VEGF, and ANG-2 in the SOCS6 low expression group were significantly increased compared to patients with high SOCS6 levels. Receiver operating characteristic (ROC) curves showed that SOCS6 could be a potential diagnostic biomarker for DR. For logistic regression, 3 models were used. It was found that SOCS6, the course of DM, SBP and DBP in model 1, IL-1β and TNF-α in model 2, and VEGF and ANG-2 in model 3 were risk factors for DR. The SOCS6 is decreased in DR patients and is related to severity and clinical outcomes, including inflammatory and angiogenic factors.

Serotype-associated immune response and network immunoclusters in children and adults during acute Dengue virus infection

The present study was designed as an exploratory investigation to characterize the overall profile of chemokines, growth factors, and pro-inflammatory/regulatory cytokines during acute DENV infection according to DENV-1, DENV-2, DENV-4 serotypes and age: children: <1–10-year-old (yo); adolescents:11–20 yo; adults 21–40 yo; and older adults: 41–75 yo. The levels of soluble immunemediators were measured in serum by high-throughput microbeads array in 636 subjects including 317 DENV-infected and 319 age-matching non-infected control (NI). Overall, most soluble mediators were increased in DENV-infected patients as compared to NI group regardless of age and DENV serotype, with high magnitude order of increase for CCL2, CXCL10, IL-1β, IFN-γ, IL1-Ra (fold change >3x), except PDGF in which no fold change was observed. Moreover, despite the age ranges, DENV-1 and DENV-4 presented increased levels of VEGF, IL-6, and TNF-α in serum but decreased levels of PDGF, while DENV-2 exhibited increased levels of CXCL8, CCL4, and IL-12. Noteworthy was that DENV-2 showed increased levels of IL-12, IL-15, IL-17, IL-4, IL-9, and IL-13, and maintained an unaltered levels of PDGF at younger ages (<1–10 yo and 11–20 yo), whereas in older ages (21–40 yo and 41–75 yo), the results showed increased levels of CCL2, IL-6, and TNF-α, but lower levels of PDGF. In general, DENV infection at younger age groups exhibited more complex network immunoclusters as compared to older age groups. Multivariate analysis revealed a clustering of DENV cases according to age for a set of soluble mediators especially in subjects infected with DENV-2 serotype. Altogether, our findings demonstrate that the profile of circulating soluble mediators differs substantially in acute DENV according to age and DENV serotypes suggesting the participation of serotype-associated immune response, which may represent a potential target for development of therapeutics and could be used to assist medical directive for precise clinical management of severe cases.

Clinical Diagnostic Value of Serum GABA, NE, ET-1, and VEGF in Chronic Obstructive Pulmonary Disease with Pulmonary Hypertension.

Pulmonary hypertension (PH) is the one of the most common complications of chronic obstructive pulmonary disease (COPD). Whereas, the associated diagnostic factors are uncertain. The present study aims to investigate useful diagnostic factors in patients with COPD and PH (COPD-PH). A total of 111 patients with COPD in Shanxi Bethune Hospital from December 2019 to December 2020 were divided into COPD (PASP≤50 mmHg) and COPD-PH groups (PASP>50 mmHg). Pulmonary function and chest CT results were collected. Routine blood, biochemical, and blood coagulation function indices were examined for all patients. Arterial blood gas analysis and serum cytokines were also measured. Differences in the distribution of the above indicators between the two groups were analyzed using binary logistic regression analysis to identify the risk factors of COPD-PH, and multiple linear regression analysis to determine the factors affecting PASP. The influencing factors and joint predictive factors of the above linear regression analysis were analyzed using the ROC curve. The area under the curve and the best cut-off value were calculated, and their predictive value and clinical significance in disease diagnosis were discussed. A total of 27 indexes with statistically significant differences between the two groups were identified (P < 0.05). Binary Logistic regression analysis showed that the factors influencing the diagnosis of pulmonary hypertension were serum GABA, NE, VEGF, BUN, and LYM% levels (P < 0.05). Multiple linear regression showed that the factors influencing PASP were serum NE, ET-1, GABA, and VEGF levels, and the goodness of fit of the model was 0.748 (P < 0.001). ROC curve showed that the AUC of the combined diagnosis of serum NE, ET-1, GABA, and VEGF levels was 0.966 (sensitivity, 87.5%; specificity, 93.65%). Serum NE and ET-1 are risk factors for COPD-PH, whereas serum GABA and VEGF are protective factors against COPD-PH. The combined diagnostic value of serum NE, ET-1, GABA, and VEGF levels was the highest.

Safety and efficacy of remote ischemic conditioning in adult moyamoya disease patients undergoing revascularization surgery: a pilot study.

Revascularization surgery for patients with moyamoya disease (MMD) is very complicated and has a high rate of postoperative complications. This pilot study aimed to prove the safety and efficacy of remote ischemic conditioning (RIC) in adult MMD patients undergoing revascularization surgery. A total of 44 patients with MMD were enrolled in this single-center, open-label, prospective, parallel randomized study, including 22 patients assigned to the sham group and 22 patients assigned to the RIC group. The primary outcome was the incidence of major neurologic complications during the perioperative period. Secondary outcomes were the modified Rankin Scale (mRS) score at discharge, at 90 days post-operation, and at 1 year after the operation. The outcome of safety was the incidence of adverse events associated with RIC. Blood samples were obtained to monitor the serum concentrations of cytokines (VEGF, IL-6). No subjects experienced adverse events during RIC intervention, and all patients could tolerate the RIC intervention in the perioperative period. The incidence of major neurologic complications was significantly lower in the RIC group compared with the control group (18.2% vs. 54.5%, P = 0.027). The mRS score at discharge in the RIC group was also lower than the control group (0.86 ± 0.99 vs. 1.18 ± 1.22, P = 0.035). In addition, the serum IL-6 level increased significantly at 7 days after bypass surgery in the control group and the serum level of VEGF at 7 days post-operation in the RIC group. In conclusion, our study demonstrated the neuroprotective effect of RIC by reducing perioperative complications and improving cerebral blood flow in adult MMD patients undergoing revascularization surgery. Thus, RIC seems to be a potential treatment method for MMD. ClinicalTrials.gov, identifier: NCT05860946.

Assessment of serum VEGF level in children type 1 diabetes mellitus

Assessment of serum VEGF level in children type 1 diabetes mellitus

Effects of low-dose ketamine infusion on vascular endothelial growth factor and matrix metalloproteinase-9 among patients with treatment-resistant depression and suicidal ideation

BackgroundEvidence indicates that vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) influence the pathophysiology of depression. However, whether low-dose ketamine regulates VEGF and MMP-9 levels and whether changes in VEGF and MMP-9 levels are associated with the antidepressant and antisuicidal effects of ketamine remained unclear. MethodsForty-eight patients with treatment-resistant depression and strong suicidal ideation (TRD-SI) were randomly assigned to a single infusion of 0.5-mg/kg ketamine or 0.045-mg/kg midazolam. The Montgomery–Åsberg Depression Rating Scale (MADRS) and Columbia-Suicide Severity Rating Scale–Ideation Severity Subscale (CSSRS-ISS) were used at baseline and subsequently at several postinfusion timepoints. VEGF and MMP-9 serum levels were analyzed at baseline and on day 3 postinfusion. ResultsAfter adjustment for baseline levels, no significant differences in VEGF (p = .912) and MMP-9 (p = .758) levels were identified on day 3 postinfusion between the study groups. Baseline VEGF levels but not MMP-9 levels were negatively associated with MADRS and CSSRS-ISS scores following infusion. DiscussionA single infusion of low-dose ketamine did not alter the VEGF and MMP-9 levels of the patients with TRD-SI. Higher baseline VEGF levels were associated with greater antidepressant and antisuicidal effects of single low-dose ketamine infusion.

Correlation between color doppler flow pattern and molecular biology in elderly patients with colon cancer

ObjectiveTo investigate the correlation between the grade and type of color Doppler flow imaging (CDFI) and tumor-related cytokines in elderly patients with colon cancer.MethodsSeventy-six elderly patients with colorectal cancer admitted to Zhejiang Provincial People’s Hospital from July 2020 to June 2022 were selected. CDFI was used to analyze the blood flow grade and distribution type of tumor tissues, and ELISA was used to detect the levels of tumor-related cytokines in serum. Preoperative clinical data were collected and analyzed, and the correlation between measured cytokine levels and CDFI analysis results was further explored.ResultsCDFI blood flow grade showed significant difference in the different lengths, invasion depths and lymph node metastasis of tumors (all P < 0.001). In addition, serum levels of TNF-α, IL-6 and VEGF also showed statistical difference in all above different tumor-related factors (all P < 0.001). Further Pearson correlation analysis showed that CDFI blood flow grade and distribution types were both significantly positively correlated with above serum cytokine levels (r > 0, all P < 0.001). Kaplan-Meier survival analysis showed that both CDFI blood flow grade and distribution types were poor prognostic factors in elderly patients with colon cancer. Regression analysis showed that serum levels of TNF-α, IL-6 and VEGF were independent risk factors for poor prognosis of colon cancer in elderly patients.ConclusionCDFI blood flow grade and tumor tissue distribution have potential significant correlations with tumor-associated cytokines in the serum of colon cancer patients. CDFI blood flow grading technique provides an important imaging method for dynamic observation of angiogenesis and blood flow changes in elderly patients with colon cancer. Abnormal changes in serum levels of tumor-related factors can be used as sensitive indicators to evaluate the therapeutic effect and prognosis of colon cancer.

The Relation of VEGFA, VEGFR2, VEGI, and HIF1A Genetic Variants and Their Serum Protein Levels with Breast Cancer in Egyptian Patients.

Breast cancer is the most common type of cancer in Egyptian females. Polymorphisms in the angiogenesis pathway have been implicated previously in cancer risk and prognosis. The aim of the current study was to determine whether certain polymorphisms in the genes of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial growth inhibitor (VEGI), and hypoxia-inducible factor-1α (HIF1A) associated with breast cancer development. The study included 154 breast cancer patients and 132 apparently healthy age-matched females as a control group. VEGFA rs25648 genotyping was performed using (ARMS) PCR technique; while VEGFR2 rs2071559, VEGI rs6478106, and HIF-1α rs11549465 were genotyped by the PCR-RFLP method. Serum levels of VEGF, VEGFR2, VEGI, and HIF1A proteins in breast cancer patients and controls were measured by ELISA. There was a significant association between the VEGFA rs25648 C allele and breast cancer risk (OR 2.5, 95% CI 1.7-3.6, p < 0.001). VEGFA rs25648 C/C genotype was statistically significantly higher in breast cancer patients vs. control (p < 0.001). Participants with the T/T and T/C VEGFR2 rs2071559 genotypes had 5.46 and 5 higher odds, respectively, of having breast cancer than those with the C/C genotype. For the VEGI rs6478106 polymorphism, there was a higher proportion of C allele in breast cancer patients vs. control (p = 0.003). Moreover, the C/C genotype of VEGI rs6478106 was statistically significantly higher in breast cancer patients vs. control (p = 0.001). There was no significant difference in genotypes and allele frequencies of HIF1A rs11549465 polymorphism between breast cancer cases and control individuals (p > 0.05). Serum levels of VEGFA, VEGI, and HIF1A were considerably greater in women with breast cancer than in the control (p < 0.001). In conclusion, the genetic variants VEGFA rs25648, VEGFR2 rs2071559, and VEGI rs6478106 revealed a significant association with increased breast cancer risk in Egyptian patients.

Alterations in choroidal vascular structures due to serum levels of vascular endothelial growth factor in patients with POEMS syndrome

A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P < 0.001). The mean luminal area to the whole choroidal area ratio at 6 months after treatment was 0.70 ± 0.03, which was significantly smaller than the ratio at baseline (0.72 ± 0.03; P < 0.001). Whole choroid and luminal area fluctuations were significantly positively correlated with fluctuations in serum VEGF levels (r = 0.626, P = 0.007 and r = 0.585, P = 0.014, respectively). Choroidal thickening induced by VEGF might be caused by increases in the choroidal vessel lumen area. These results may offer insights into the pathogenesis of POEMS syndrome and the role of serum VEGF in choroidal vascular structure, which may apply to other ocular diseases.

P-631 Alleviating effects of EGCG on ovarian hyperstimulation syndrome and the potential modulating mechanism through the VEGF pathway

Abstract Study question What are the underlying mechanisms of EGCG to alleviate Ovary hyperstimulation syndrome (OHSS)? Summary answer EGCG inhibited VEGF via TGF-β1 classical-SMAD pathway and 67LR-mediated CREB pathway and could reduce the ovarian inflammatory effect and attenuated OHSS progress in rat model. What is known already Ovarian hyperstimulation syndrome (OHSS) is one of the most severe complications of COH during IVF treatment. The pathophysiology of OHSS is characterized by increased capillary permeability, VEGF is an important mediator in OHSS, and serum VEGF levels have been shown to correlate with OHSS severity. (-)-epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active polyphenolic catechin in green tea and has been reported to have multiple effects in humans. Many research indicated that in many pathological processes, EGCG could inhibit VEGF and its receptor expression and have an angiogenesis effect. Herein, EGCG might have a therapeutic effect on OHSS. Study design, size, duration We investigated the role of EGCG in OHSS in vitro and in vivo. The primary human granulosa-lutein(hGL) cells and human granulosa-like tumor (KGN) cell line were cultured and treated with different concentrations of EGCG for 24 hours. Animal OHSS model was established in SD rats by injection of pregnant mare serum gonadotropin (PMSG), and randomly assigned to receive vehicle only or EGCG for 3 days. All experiments were performed 3-8 times for comparisons. Participants/materials, setting, methods The effect of EGCG on KGN and hGL cells was determined by MTT assay. The body weight of rats was measured every day, and the ovary size was measured after removal, the permeability was determined by Evans-blue. The serum estrogen and VEGF level in rats were detected by ELISA. RNA and protein expressions of VEGF, VEGFR-2, TGF-β, and TβR II were detected by qPCR and Western-blotting and immunostaining in vitro and in vivo experiments. Main results and the role of chance Our study demonstrated that administration of EGCG attenuated the development of OHSS in rats, as shown by histological examination and ovarian weight and morphology. The ovary weight was significantly decreased in the EGCG treatment group compared with the OHSS group (147.9 vs 206.5 mg). Additionally, compared to OHSS rats, EGCG treated rats exhibit downregulated ovarian VEGF expression determined by IHC and RT-qPCR. VEGF and E2 protein levels significantly decrease in the serum of the EGCG treatment group. EGCG exerted inhibitory effects on cell growth only in high dose (50uM) and longtime (48h) treatment in KGN and hGL cells. In KGN cells and hGL cells, EGCG significantly reduces the expression of VEGF and TGF-β at the RNA and protein levels. Furthermore, EGCG inhibits TGF-β1-induced VEGF production and secretion in KGN cells by suppressing TGF-β expression and its traditional Smad signaling pathway. EGCG also downregulates VEGF expression through the 67-kDa laminin receptor-mediated PKA-CREB pathway. Limitations, reasons for caution EGCG has been reported to employ a wide range of biological effects. Therefore, its suppressive effects on VEGF and TGF-β signaling pathway might be part of the pharmacological mechanisms to alleviate Ovary hyperstimulation syndrome. Further studies are also needed to explore the therapeutic mechanisms of melatonin from other perspectives. Wider implications of the findings Our findings add mechanistic insight in support of using EGCG as an adjuvant therapy in the management of OHSS. EGCG shows the potential to act as a novel alternative therapeutic drug to treat OHSS. Daily intake of green tea might be beneficial for women under COH to prevent OHSS. Trial registration number Not applicable

Serum vascular endothelial growth factor associated with the progression of granulosa cell tumor: a report of two cases

BackgroundGranulosa cell tumors (GCTs) account for approximately 2% of ovarian malignancies and are considered a rare type of ovarian cancer. GCTs are characterized by irregular genital bleeding after menopause due to female hormone production as well as late recurrence around 5–10 years after initial treatment. In this study, we investigated two cases of GCTs to find a biomarker that can be used to evaluate the treatment and predict recurrence.Case presentationCase 1 was a 56-year-old woman who presented to our hospital with abdominal pain and distention. An abdominal tumor was found, and GCTs were diagnosed. Serum vascular endothelial growth factor (VEGF) levels decreased after surgery. Case 2 involved a 51-year-old woman with refractory GCTs. Carboplatin–paclitaxel combination therapy and bevacizumab were administered after the tumor resection. After chemotherapy, a decline in VEGF levels was observed, but serum VEGF levels increased again with disease progression.ConclusionsVEGF expression may be of clinical importance in GCTs as a clinical biomarker for disease progression, which may be used to determine the efficacy of bevacizumab against GCTs.

Angiogenic potential of circulating peripheral blood neutrophils in kidney cancer

The role of neutrophils in kidney cancer is currently being studied. Their role in carcinogenesis is ambiguous. As one of the most abundant blood leukocytes, neutrophils play an important role in cancer progression through multiple mechanisms, including promotion of angiogenesis, immunosuppression, and cancer metastasis. Neutrophils synthesize and release pro-angiogenic factors that are able to directly or indirectly stimulate the growth and migration of endothelial cells, which in turn causes the formation of new blood vessels from pre-existing ones. The production of various factors by neutrophils, including proangiogenic ones, is mediated by the expression of the genes of these molecules. Functional heterogeneity is characterized by differences in neutrophil gene expression patterns. The aim of this study was to evaluate the angiogenic potential of circulating neutrophils in kidney cancer. The object of the study were blood neutrophils of patients with verified clear cell kidney cancer at stage I (T1N0M0G1, n = 28, median age 60), stage II (T2N0M0G2, n = 15, median age 61) and stage III (T3N0M0G2, n = 15, median age 63) before surgery. The control group consisted of apparently healthy donors (n = 15, median age 54). Serum levels of IL-8 and VEGF-A were assessed by enzyme immunoassay. Expression of the CXCL8 and VEGF-A genes in circulating neutrophils was determined by reverse transcription quantitative PCR. As a result of our study, an increase in the level of IL-8 and VEGF-A in the blood serum of patients with kidney cancer in all studied groups compared with the control group was revealed. We observed a direct correlation between serum levels of IL-8 and VEGF-A in patients with kidney cancer (r = 0.429; p = 0.016), which confirms the relationship of these angiogenic factors. A significant increase in CXCL8 gene expression by circulating neutrophils was found in patients on II (2.91, Q0.25-Q0.75: (1.296-4.99), p = 0.02) and III (1.93, Q0.25-Q0.75: (0.755-11.36, p = 0.014) stages of kidney cancer compared with the control group (1.50, Q0.25-Q0.75: (0.80-4.05)). However, VEGF-A gene expression by circulating neutrophils did not differ from those in the control group. Blood neutrophils in kidney cancer exercise their angiogenic potential through the production of IL-8.

Proinflammatory cytokines VEGFA, IL-6, IL-8 as markers of hepatotoxicity after COVID-19

The mechanism of hepatocellular liver damage after COVID-19 is a multifactorial process. The most widely discussed causes are cytolytic liver damage due to the inflammatory response after COVID-19, drug-induced hepatotoxicity and direct cytotoxic effect of the virus. There are observations that SARSCoV-2 infection causes hepatitis B virus reactivation, but little has been described about the interaction between hepatitis C virus and SARS-CoV-2. The course of coronavirus infection is associated with marked expression of proinflammatory cytokines, participants in the multisystem inflammatory response, IL-1β, IL-6, IL-8, IL-18, MCP-1, TNFα, which contribute significantly to the observed early and late liver function impairment. The aim of the study was to evaluate the role of proinflammatory cytokines (VEGFA, IL-8, IL-6, MCP-1, TNFα, IL-18) as additional markers of hepatotoxicity after COVID-19. The study was performed between March and August 2022. Patients were divided into 2 groups: Group 1 – with increased aminotransferases against the background of treatment from COVID-19 and/or in the following 3-6 months after the disease without viral liver damage (n = 42), Group 2 – patients with co-infection (chronic viral hepatitis C (HCV) and COVID-19 (n = 26). The levels of cytokines – VEGF-A, IL-6, IL-8, MCP-1, IL-18, TNFα in blood serum were estimated by enzyme immunoassay method. Statistical analysis was performed using StatTech v. 3.1.4. The results of the study revealed a comparable increase in the level of transaminases and C-reactive protein in both groups, significantly different from the reference values. Direct correlations of moderate strength (linear Spearman correlation) were found between the following cytokines: TNFα-MCP-1 (R = 0.559; p = 0.001), TNFα-VEGFA (R = 0.400; p = 0.002), TNFα-IL-6 (R = 0.503; p = 0.001). We diagnosed a significant increase in serum VEGFA levels in group 1 patients (hepatotoxicity after COVID-19) (Me (Q0.25-Q0.75): 522 (250 to 1002), p = 0.001) and in group 2 patients (HCV + COVID-19) (Me 1196, Q0.25-Q0.75: (73 to 432). Similar trend with the level of IL-6, IL-8, exceeding the values of cytokines in healthy donors and significantly higher than in group 2 patients. Identified correlations between inflammatory cytokines prove unidirectional changes in the functioning of the regulatory network controlling immune virus-induced reactions.

Immunological signature of patients with thymic epithelial tumors and Good syndrome: Correlation with clinical outcome.

e20648 Background: Thymic epithelial tumors (TETs) are extremely rare and heterogenous neoplasms, associated with immune dysregulation. Recognized prognostic factors are TNM stage and the Masaoka-Koga classification. To the best of our knowledge, no study has been conducted to investigate the correlation between immunophenotype, level of cytokines, chemochines and clinical outcome in TETs patients. The aim of this study was to evaluate the correlation of immunological signature and long-term outcome in patients with TETs and Good Syndrome (GS). Methods: From May 2019 to October 2022, consecutive patients with TETs and GS, referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR) of Federico II of Naples, were enrolled. The immunophenotype of monocytes, neutrophils, eosinophils, CD4+ T cells, CD8 + T cells, B-cells, NK cells and NKT-cells, T regulatory cells, and the evaluation of serum levels of cytokines, chemokines and growth factors were assessed using the 8-color immunophenotyping kit, Treg detection kit and pre-formed Kits by Bioplex multiplex, respectively. D’Agostino-Pearson normality test was used to evaluate whether the continuous data were normally distributed, and a two-tailed t-test for independent samples was used. Overall survival (OS) analysis was performed generating Kaplan-Meier curves and Cox Univariate models for the considered categorical stratifications. p-values &lt; 0.05 were considered statistically significant. Results: A total of 24 consecutive TETs patients were included in the study: 13 (54.17%) patients were male and 11 (48.83%) were female, with a median age of 54.96 ± 9.6 years. Tumor histology included 20 thymoma, and 4 thymic carcinoma. Autoimmune diseases were found in 13 patients all of whom had thymoma. At the time of this analysis, 5 (20.83%) patients had no evidence of disease (NED) by imaging and were in follow-up, 17 (70.83%) patients were still alive. The analysis of leucocytes did not show statistically significant association with clinical outcome of TETs patients. On the contrary, a statistically significant correlation between serum concentration of IL-6 and OS was found with lower levels of IL-6 associated with poorer prognosis (HR: 9.654; p = 0.016). In addition, we found a statistically significant reduction of IL-2 (p = 0.04), IL-15 (p = 0.048), IL-5 (p = 0.03) and VEGF (p = 0.01) serum levels in patients with evidence of disease, as compared to NED patients. Conclusions: Overall, these findings suggest that measurement of IL-6 levels may be a useful parameter for identifying TETs patients with GS who have more aggressive diseases. Our preliminary data may be useful in the clinical management of this complex disease. Further studies are needed to better understand the pathophysiology and clinical implications of immunophenotype alterations in TETs patients.

Retrospective efficacy analysis of olaparib combined with bevacizumab in the treatment of advanced colorectal cancer

Colorectal cancer (CRC) is a highly prevalent malignancy of the digestive tract worldwide, characterized by a significant morbidity and mortality rate and subtle initial symptoms. Diarrhea, local abdominal pain, and hematochezia occur with the development of cancer, while systemic symptoms such as anemia and weight loss occur in patients with advanced CRC. Without timely interventions, the disease can have fatal consequences within a short span. The current therapeutic options for colon cancer include olaparib and bevacizumab, which are widely utilized. This study intends to evaluate the clinical efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC, hoping to provide insights into advanced CRC treatment.To investigate the retrospective efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC.A retrospective analysis was conducted on a cohort of 82 patients with advanced colon cancer who were admitted to the First Affiliated Hospital of the University of South China between January 2018 and October 2019. Among them, 43 patients subjected to the classical FOLFOX chemotherapy regimen were selected as the control group, and 39 patients undergoing treatment with olaparib combined with bevacizumab were selected as the observation group. Subsequent to different treatment regimens, the short-term efficacy, time to progression (TTP), and incidence rate of adverse reactions between the two groups were compared. Changes in serum-related indicators [vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9), cyclooxygenase-2 (COX-2)] and tumor markers [human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199)] levels before and after treatment were compared between the two groups at the same time.The objective response rate was discovered to be 82.05%, and the disease control rate was 97.44% in the observation group, which were significantly higher than the respective rates of 58.14% and 83.72% in the control group (P < 0.05). The median TTP was 24 mo (95%CI: 19.987-28.005) in the control group and 37 mo (95%CI: 30.854-43.870) in the observation group. The TTP in the observation group was significantly better than that in the control group, and the difference held statistical significance (log-rank test value = 5.009, P = 0.025). Before treatment, no substantial difference was detected in serum VEGF, MMP-9, and COX-2 levels and tumor markers HE4, CA125, and CA199 levels between the two groups (P > 0.05). Following treatment with different regimens, the above indicators in the two groups were remarkably promoted (P < 0.05), VEGF, MMP-9, and COX-2 in the observation group were lower than those in the control group (P < 0.05), and HE4, CA125, and CA199 levels were also lower than those in the control group (P < 0.05). Vis-à-vis the control group, the total incidence of gastrointestinal reactions, thrombosis, bone marrow suppression, liver and kidney function injury, and other adverse reactions in the observation group was notably lowered, with the difference considered statistically significant (P < 0.05).Olaparib combined with bevacizumab in the treatment of advanced CRC demonstrates a strong clinical effect of delaying disease progression and reducing the serum levels of VEGF, MMP-9, COX-2 and tumor markers HE4, CA125 and CA199. Moreover, given its fewer adverse reactions, it can be regarded as a safe and reliable treatment option.

Inhibition of tumor-specific angiogenesis by AS1411 aptamer functionalized Withaferin A loaded PEGylated nanoliposomes by targeting nucleolin

Angiogenesis is a vital process for tumor growth and metastasis. Inhibition of angiogenesis is a promising strategy in cancer treatment. In this study, we analyzed the anti-angiogenic activity of AS1411 functionalized Withaferin A encapsulated PEGylated nanoliposomes (ALW) using both in vitro and in vivo models. AS1411 aptamer functionalized nanoliposomes are an efficient drug delivery system for carrying chemotherapeutic agents to target cancer cells, and Withaferin A (WA) is a steroidal lactone known for potent anti-angiogenic activity. ALW showed significant inhibition in the migration and tube formation of endothelial cells, which are critical events in angiogenesis. In vivo angiogenesis study using ALW showed remarkable inhibition of tumor-directed capillary formation by altered serum cytokines, VEGF, GM-CSF, and NO levels. ALW treatment downregulated the gene expression of Matrix metalloproteinase (MMP)-2, MMP-9, VEGF, NF-kB and upregulated the expression of tissue inhibitor of metalloproteinase (TIMP)-1. Our results demonstrate that ALW inhibits tumor-specific angiogenesis by gene expression of NF-κB, VEGF, MMP-2, and MMP-9. The present study shows that using ALW can offer an attractive strategy for inhibiting tumor angiogenesis.

One Single Tube Reaction of Aptasensor-Based Magnetic Sensing System for Selective Fluorescent Detection of VEGF in Plasma.

In this study, a simple, easy and convenient fluorescent sensing system for the detection of the vascular endothelial growth factor (VEGF) based on VEGF aptamers, aptamer-complementary fluorescence-labeled probe and streptavidin magnetic beads was developed in one single tube. The VEGF is the most important biomarker in cancer, and it is investigated that the serum VEGF level varied according to the different types and courses of cancers. Hence, efficient quantification of VEGF is able to improve the accuracy of cancer diagnoses and the precision of disease surveillance. In this research, the VEGF aptamer was designed to be able to bind with the VEGF by forming G-quadruplex secondary structures; then, the magnetic beads would capture the non-binding aptamers due to non-steric interference; and finally, the fluorescence-labeled probes were hybridized with the aptamers captured by the magnetic beads. Therefore, the fluorescent intensity in the supernatant would specifically reflect the present VEGF. After an overall optimization, the optimal conditions for the detection of VEGF were as followed, KCl, 50 μM; pH 7.0; aptamer, 0.1 μM; and magnetic beads, 10 μL (4 μg/μL). The VEGF could be well quantified within a range of 0.2-2.0 ng/mL in plasma, and the calibration curve possessed a good linearity (y = 1.0391x + 0.5471, r = 0.998). The detection limit (LOD) was calculated to be 0.0445 ng/mL according to the formula (LOD = 3.3 × σ/S). The specificity of this method was also investigated under the appearance of many other serum proteins, and the data showed good specificity in this aptasensor-based magnetic sensing system. This strategy provided a simple, sensitive and selective biosensing platform for the detection of serum VEGF. Finally, it was expected that this detection technique can be used to promote more clinical applications.

Efficacy and safety of intraperitoneal bevacizumab combined with hyperthermic intraperitoneal chemotherapy in the treatment of patients with ovarian cancer and peritoneal effusion and the effect on serum lncRNA H19 and VEGF levels

Peritoneal effusion is a common event in ovarian cancer (OC) patients. LncRNA H19 and vascular endothelial growth factor (VEGF) are implicated in cancer progression. The study evaluated the curative effect and safety of bevacizumab combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in OC patients with peritoneal effusion and the effect on serum lncRNA H19/VEGF levels. Totally 248 OC patients with peritoneal effusion were treated with intraperitoneal bevacizumab + HIPEC (observation group) or abdominal paracentesis without HIPEC (control group). The clinical efficacy, quality of life, and adverse reactions were evaluated after two treatment cycles. The serum lncRNA H19 and VEGF levels pre-/post-treatment were determined by RT-qPCR and ELISA. The observation group exhibited better clinical efficacy than the control group, evidenced by a higher partial response rate, response rate, and disease control rate. The observation group exhibited reduced physical/cognitive/role/social/emotional function scores and total adverse reactions. LncRNA H19/VEGF levels showed no significant difference between the two groups before treatment but were significantly downregulated in the observation group after treatment. Summarily, intraperitoneal bevacizumab + HIPEC has significant efficacy in treating peritoneal effusion, improves the quality of life, and reduces serum lncRNA H19 and VEGF levels in OC patients, with fewer adverse reactions and higher safety. Impact statement What is already known on this subject? The utilization of hyperthermic intraperitoneal chemotherapy (HIPEC) as an emerging treatment option for abdominal malignancies has garnered the attention of numerous researchers over the years, which has significant clinical effects on peritoneal effusion in ovarian cancer and can control patients’ conditions and improve their signs and symptoms to a certain extent. What do the results of this study add? In this paper, we investigated the efficacy and safety of intraperitoneal bevacizumab combined with hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal effusion in ovarian cancer. Meanwhile, we compared serum lncRNA H19 and VEGF levels before and after treatment. What are the implications of these findings for clinical practice and/or further research? Our findings may provide a clinically worthy method for the treatment of peritoneal effusion in ovarian cancer. The treatment method reduces serum lncRNA H19 and VEGF levels in patients, which provides a theoretical basis for further research.

Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway

Ethnopharmacological relevanceThe Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides ‘Chuanxiong’, Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's “Yilin Gaicuo” in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. Aim of the studyThis study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. Materials and methodsSixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. ResultsMany effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). ConclusionsThe mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.