Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.

Mendelian Randomization Study of Causal Relationship between Inflammatory Factors and Vascular Dementia and Chinese Herbal Medicines Screening for Prevention and Treatment

Objective: This study aims to examine the causal relationship between inflammatory factors and the probability of developing vascular dementia (VD) using Mendelian Randomization (MR) and Chinese herbal medicine prediction method, and to screen potential Chinese herbal medicines for the prevention and treatment of VD. Methods: Single nucleotide polymorphisms (SNPs) that exhibit a strong association with vascular dementia (VD) were identified as instrumental variables from the summary statistics of genome-wide association studies (GWAS). The primary analytical method employed was inverse variance weighting (IVW), while auxiliary analyses included the MR-Egger method, weighted median method, simple model, and weighted model. A two-way Mendelian randomization analysis was conducted to assess the causal relationship between inflammatory factors and the risk of VD, thereby identifying the key inflammatory factors involved. The MR-Egger intercept test and Cochran’s Q test were employed to assess the horizontal polymorphism and heterogeneity of instrumental variables. A sensitivity analysis was conducted by excluding one method at a time. Ultimately, based on key inflammatory factors, predictions for the prevention and treatment using traditional Chinese medicine were made, along with the screening of homologous herbal remedies. Results: Based on the results of the forward MR, the probability of developing VD was elevated when the inflammatory factors CXCL10 and CXCL5 were expressed at higher levels, whereas the probability of developing VD decreased as the expression levels of IL-13 and IL-20RA increased. These findings were supported by the assessment of pleiotropy, heterogeneity, and sensitivity. The results of the reverse MR analysis showed that there was no causal relationship between VD, as an exposure dataset, and these four inflammatory factors. According to the key inflammatory factors, 37 Chinese herbal medicines such as Siraitia grosvenorii were selected. Their characteristics including four natures, five flavors, channel tropism and treatment efficiency were cold, warm, neutral, pungent, sweet, bitter, lung meridian, spleen meridian, liver meridian, kidney meridian and clearing heat. Among them, Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi were all medicine and food homologous Chinese herbal medicines. Conclusions: The increase of CXCL10 and CXCL5 expression levels can increase the risk of VD, and the increase of IL-13 and IL-20 RA expression levels can reduce the risk of VD. Siraitia grosvenorii and other Chinese herbal medicines might be potential sources of therapeutic drugs for the treatment of VD. Medicine and food homologous Chinese herbal medicines, such as Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi, may help the elderly population with corresponding Traditional Chinese Medicine (TCM) constitutions to prevent VD.

Diagnostic value of serum vascular endothelial growth factor and interleukin-17 in primary hepatocellular carcinoma

BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldwide.AIM To investigate the expression levels of serum vascular endothelial growth factor(VEGF)and interleukin(IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients’clinical characteristics.METHODS The study included 50 patients with confirmed PHC who visited Wuhan Han-yang Hospital from January 2021 to January 2022,and 50 healthy individuals from the same period served as the control group.Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay,and their diagnostic value was assessed using receiver operating characteristic(ROC)curves.Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels.Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics.RESULTS Serum VEGF and IL-17 levels were significantly higher in the study group com-pared to the control group(P<0.05).No significant association was observed between serum VEGF and IL-17 levels and gender,age,combined cirrhosis,tumor diameter,or degree of differentiation(P>0.05).However,there was a significant relationship between clinical TNM stage,tumor metastasis,and serum VEGF and IL-17 levels(P<0.05).Correlation analysis revealed a positive correlation between serum VEGF and IL-17(P<0.05).ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC.CONCLUSION Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals.Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage,and there was a significant positive correlation between VEGF and IL-17.These biomarkers may serve as valuable reference in-dicators for the early diagnosis and treatment guidance of PHC.

Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer

AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.

Scalp electroacupuncture at the Baihui acupoint (DU 20) improves functional recovery in rats with cerebral ischemia Association with increased expression of vascular endothelial growth factors

In this study, we induced cerebral infarction in rats by occluding the right middle cerebral artery, and tested the effects of electroacupuncture at the Baihui acupoint （DU 20）. Motor and sensory function was tested using Garcia’s scale and motor weakness grading, and the expression of vascular endothelial growth factor in the brain was quantified using immunoblotting and immunohistochemistry. We found that scalp electroacupuncture at DU 20 significantly improved motor performance and sensory function in rats with stroke, and this was accompanied by an increased expression of vascular endothelial growth factor in the ischemic brain tissue and peri-ischemic area. In addition, Pearson correlation analysis showed that the improvements in functional recovery were correlated with the increased expression of vascular endothelial growth factor.

Elevated Vascular Endothelial Growth Factor Level in Association with Mean Platelet Volume Are Emerging Risk Factors for Vascular Complications in T2DM Patients

Increasing evidence in both experimental and clinical studies suggests oxidative stress (OS) plays a major role in the pathogenesis of type 2 diabetes mellitus and its complications. In a physiological condition, appropriate levels of ROS, generated either in restricted amounts or transient fashion, are required to promote physiological angiogenesis and homeostatic maintenance of healthy vasculature. Uncontrolled continuous ROS production will ultimately contribute to pathology and cause tissue damage. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF) which plays a key role in diabetic endothelial dysfunction, which ultimately leads to pathogenesis of vascular complications. As VEGF is released by activated platelets, hence platelet activation could be the source of VEGF in plasma samples. Increased platelet activity is emphasized to play a role in the development of vascular complications in T2DM patients and platelet volume, a marker of the platelet function and activation, is measured as mean platelet volume (MPV). Therefore, we aimed to investigate the association between plasma VEGF levels and MPV levels that may lead to vascular complications. A case-control study of one hundred patients with T2DM (n = 100) and thirty control subjects (n = 30) were screened from different areas of West Bengal. All procedures were done with the informed consent of participants. Elevated VEGF level was found in T2DM patients (526.8 ± 34.3 pg/ml) compared to healthy controls (317.9 ± 12.9 pg/ml) which was statistically significant. T2DM patients had higher MPV (12.5 ± 0.2 fl) compared to controls (11.4 ± 0.2 fl). Thus the present study showed a significant association between VEGF level in plasma and MPV indicating the severity of vascular complications. Hence, in conclusion, it suggested that VEGF levels along with MPV are a reliable biomarker for evaluating the development and progression of vascular complications.

Inhibitory effect of vascular endothelial growth factors-targeted small interfering RNA on proliferation of gastric cancer cells

AIM： To examine the effects of vascular endothelial growth factor （VEGF）-targeted small interfering RNA （siRNA） on proliferation of gastric cancer cellsin vitro.METHODS： Several siRNAs were transfected into human gastric cancer cell line SGC-7901 with Lipofectamine 2000. Cells not transfected with LipofectamineTM 2000 or scrambled （SCR） siRNA served as controls. The inhibitory effect of siRNA on the expression of VEGF mRNA and protein was detected by RT-PCR and ELISA. MTT assay was used to examine the inhibition rate of cell growth.The change in cell cycling of siRNA-treated cells was detected by flow cytometry.RESULTS： siRNA targeting human VEGF effectively inhibited the proliferation of gastric cancer cell lineSGC-7901 and the distribution of cell cycle. The percentage of G0/G1 phase was significantly higher in siRNA1- and siRNA2-transfected cells than in control cells.The expression of VEGF mRNA was significantly inhibited in siRNA1- and siRNA2-transfected cells compared with that in control cells. VEGF protein notably decreased in siRNA-transfected cells, but had no effect on SCR siRNA.CONCLUSION： VEGF siRNA inhibits proliferation of gastric cancer cells in vitro.

Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy

AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of conbercept.METHODS:This study included 72 PDR patients and 8 cataract patients as controls.PDR patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 mL)injection and pars plana vitrectomy(PPV)performed.Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ELISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was studied.RESULTS:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all intervals.Liquid chromatography tandem mass spectrometry(LC-MS/MS)identified differentially expressed proteins between preand post-IVC samples.GO and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling pathways.PPI analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ELISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COL1A1,and ACTB,with significant changes in the IVC groups.CONCLUSION:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with PDR.Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response,stress response,and cellular metabolism.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

BACKGROUND The incidence and mortality of colorectal cancer(CRC)are among the highest in the world,and its occurrence and development are closely related to tumor neovascularization.When the balance between pigment epithelium-derived factors(PEDF)that inhibit angiogenesis and vascular endothelial growth factors(VEGF)that stimulate angiogenesis is broken,angiogenesis is out of control,resulting in tumor development.Therefore,it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.AIM To investigate the expression and significance of PEDF,VEGF,and CD31-stained microvessel density values(CD31-MVD)in normal colorectal mucosa,adenoma,and CRC.METHODS In this case-control study,we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022.Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy(normal control group),50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy(adenoma group),and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery(CRC group).An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens,analyze their differences,study the relationship between the two and clinicopathological factors in CRC group,record CD31-MVD in the three groups,and analyze the correlation of PEDF,VEGF,and CD31-MVD in the colorectal adenoma group and the CRC group.The F test or adjusted F test is used to analyze measurement data statistically.Kruskal-Wallis rank sum test was used between groups for ranked data.The chi-square test,adjusted chi-square test,or Fisher's exact test were used to compare the rates between groups.All differences between groups were compared using the Bonferroni method for multiple comparisons.Spearman correlation analysis was used to test the correlation of the data.The test level(α)was 0.05,and a two-sided P<0.05 was considered statistically significant.RESULTS The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group,adenoma group,and CRC group(100%vs 78%vs 50%,χ^(2)=34.430,P<0.001;++~++vs+~++vs-~+,H=94.059,P<0.001),while VEGF increased gradually(0%vs 68%vs 96%,χ^(2)=98.35,P<0.001;-vs-~+vs++~+++,H=107.734,P<0.001).In the CRC group,the positive expression rate of PEDF decreased with the increase of differen-tiation degree,invasion depth,lymph node metastasis,distant metastasis,and TNM stage(χ^(2)=20.513,4.160,5.128,6.349,5.128,P<0.05);the high expression rate of VEGF was the opposite(χ^(2)=10.317,13.134,17.643,21.844,17.643,P<0.05).In the colorectal adenoma group,the expression intensity of PEDF correlated negatively with CD31-MVD(r=-0.601,P<0.001),whereas VEGF was not significantly different(r=0.258,P=0.07).In the CRC group,the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF(r=-0.297,P<0.05;r=-0.548,P<0.05),while VEGF expression intensity was positively related to CD31-MVD(r=0.421,P=0.002).CONCLUSION It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Meta-Analysis of Risk Factors of Vascular Cognitive Disorder in Acute Cerebral Infarction Patients

Objectives: To identify the main risk factors of vascular cognitive impairment in patients with acute cerebral infarction by Meta-analysis, and provide references for the effective prevention of the cognitive impairment in stroke patients. Methods: To retrieve the observational research literatures that refer to the risk factors of vascular cognitive impairment in patients with ischemic stroke, which are published on China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Chinese databases. The screening and data extraction of these literatures are independently completed by two researchers, who also give the quality evaluation of the literatures according to the evaluation criterion of the Australian JBI Evidence-Based Health Care Center. Then, Meta-analysis is conducted by using Revman5.3 software. Results: There are twenty-eight articles selected from 1507 literatures, with a total of 10,711 cases and 50 risk factors included. Among them, there are combined effects of ten factors which have statistical significance, such as infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetes mellitus, age, history of cerebral infarction, hyperlipoidemia and education level. The relational merging OR value and 95% CI between the type-variable factors and cognitive impairment are 3.25 (1.84, 5.76);2.98 (2.58, 3.45);2.79 (1.69, 4.59);2.35 (1.93, 2.85);2.25 (1.86, 2.71);2.14 (2.10, 2.18);1.82 (1.62, 2.03);1.54 (1.24, 1.92);1.45 (1.34, 1.56);0.83 (0.78, 0.89). Conclusion: Infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetesmellitus, age, history of cerebral infarction, hyperlipoidemia and low education level are the main risk factors for vascular cognitive impairment in patients with acute cerebral infarction. Clinical nursing staff should include it into the routine assessment of patients with acute cerebral infarction and actively prevent and intervene.

Logistic regression analysis on risk factors for vascular dementia following cerebral infarction in 403 patients from Chongqing City Hospital and family follow-up studies

BACKGROUND： Studies have demonstrated that the risk factors of vascular dementia following stroke are greatly different in region, race and other aspects. OBJECTIVE： To analyze the conditions and incidental risk factors of vascular dementia in patients with acute cerebral infarction from Chongqing City. DESIGN： Case analysis. SETTING： Department of Neurology, Daping Hospital, Third Military Medical University of Chinese PLA. PARTICIPANTS： Altogether 546 inpatients with acute ischemic stroke admitted to Department of Neurology, Daping Hospital, Third Military Medical University of Chinese PLA between May 1999 and December 2002 were involved in this study. The involved patients, including 295 males and 251 females, aged 55 - 94 years, dwelled in Chongqing over 5 years. They were admitted to hospital within 48 hours of attack of acute ischemic stroke, and survived for over 3 months. Informed consents were obtained from all the involved subjects. METHODS： ① Following the same standard, cognitive and social function evaluations were conducted by one physician on admission and 3 months after admission, Unified questionnaire, consisting of general characteristics, vascular risk factors, stroke characteristics, neurological physical sign, and other 28 factors of involved subjects, was used in all the patients. According to the investigation results, the patients were assigned into 2 groups： dementia group and non-dementia group. ②Ischemic stroke was diagnosed according to acute ischemic brain disorder 〉 24 hours and CT or MRI imageology.③ Neurophysiological examination was conducted in all the patients at 7 to l0 days after stroke （score was two SD less than or equaled to normal level was considered as abnormal）. ④Diagnosis and statistics of dementia were carried out with Mini-Mental State Examination and The Diagnostic and Statistical Manual of Mental Disorders-Ⅳ （published by American Psychiatric Association） on admission and 3 months after admission. Neurologic deficit scoring was carried out with the National Institutes of Health Stroke Scale. ⑤ Chi-square test was used for categorical variable, and t test for quantitative variable between dementia group and non-dementia group. Dementia-related factors were performed multiple-factor Logistic regression model analysis. MAIN OUTCOME MEASURES： Incidence of dementia and dementia-related risk factors of patients. RESULTS： Altogether 546 patients with stroke were involved in this study, 403 of them participated in the final analysis, and 143 dropped out. A total of 342 were followed-up in the hospital and 61 at home. At 3 months after cerebral infarction, vascular dementia occurred in 87 （21.6%） of 403 patients. The main risk factors were age （OR 1.179; 95%CI 1.130 - 1.230）, low education level （OR 1.806; 95%CI 1.024 - 3.186）, daily alcohol drinking （OR 3.447; 95%（1/ 1.591 - 7.468）, stroke history （OR 2.531; 95%CI 1.419 - 4.512）, atrial fibrilation（OR 3.475; 95%CI 1.712 - 7.057）, dysphonia （OR 5.873; 95%6/2.620 - 13.163） and left carotid artery infarction （OR 1.975; 95%（1/1.152 - 3.388）. CONCLUSION： The incidence of vascular dementia is determined by synthetic action of multiple risk factors. Dysphonia is the most important influencing factor.

Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme:a systematic review going beyond pathologic implications

Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.

Vascular endothelial growth factor pathway’s influence on bevacizumab efficacy in metastatic colorectal cancer treatment

In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,including bevacizumab,in treating patients with colorectal cancer(CRC).Through neutralization of vascular endothelial growth factor(VEGF),bevacizumab inhibits tumor angiogenesis,impairing neovascularization and thereby depriving the tumor of essential nutrients and oxygen.Conversely,PD-L1 binding to VEGF receptor 2 promotes angiogenesis,supporting tumor vasculature.The interplay between these pathways complicates the assessment of bevacizumab’s efficacy in cancer therapy,notably in CRC,where VEGF and PD-L1 significantly affect treatment response.This review examines metastatic CRC treatment strategies,focusing on bevacizumab’s mechanism of action and the role of PD-L1 in this therapeutic context.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Hemostatic mechanism of the effect of Jianpi Yiqi Shexue decoction on vascular factors in immune thrombocytopenia model mice

Objective: To explore the hemostatic mechanism of Jianpi Yiqi Shexue decoction(JYSD) by regulating vascular factors in an immune thrombocytopenia(ITP) mouse model.Methods: An ITP mouse model was established by the passive-immune modeling method, and interventional drugs used were prednisone tablets and JYSD. The platelet count;vascular activity-related factors v WF, VCAM-1, and TM;and VEGF and b FGF were used as observational indicators.Results: On the 8th day of administration, compared with the model group, platelet counts in the prednisone and JYSD groups increased(both P <.001). Compared with the control group, the levels of v WF, VCAM-1, and TM in the other groups were lower(all P <.05). The VCAM-1 level in the JYSD group was higher than that in the prednisone group(P =.012), but without significant difference compared with the model group(P =.051). The TM level in the JYSD group was the lowest(vs. the model group,P =.047;vs. the prednisone group, P =.006). Compared with the control group, the IOD values of VEGF and b FGF in the other three groups were lower(all P <.01). The IOD values of VEGF in the prednisone and JYSD groups were both higher than those in the model group(P =.002 and P <.001, respectively). The IOD values of b FGF among the model, prednisone, and JYSD groups were not statistically significant(P >.05).Conclusion: A vascular factor disorder is involved in the pathogenesis of ITP. JYSD can increase the platelet count, upregulate VEGF expression, and reduce the TM level. JYSD has the same effect as prednisone tablets in regulating platelet, v WF, VEGF, and b FGF, with a stronger effect in normalizing VCAM-1 and TM levels. The hemostatic mechanism of JYSD is closely related to the effective balance of vascular factors.

Nomogram for predicting short-term response to anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration:An observational study

BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes.AIM To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response.METHODS In this study,65 eyes of exudative AMD patients after anti-VEGF treatment for≥1 mo were observed using optical coherence tomography angiography.Patients were classified into non-responders(n=22)and responders(n=43).Logistic regression was used to determine independent risk factors for treatment response.A predictive model was created using the Akaike Information Criterion,and its performance was assessed with the area under the receiver operating characteristic curve,calibration curves,and decision curve analysis(DCA)with 500 bootstrap re-samples.RESULTS Multivariable logistic regression analysis identified the number of junction voxels[odds ratio=0.997,95%confidence interval(CI):0.993-0.999,P=0.010]as an independent predictor of positive anti-VEGF treatment outcomes.The predictive model incorporating the fractal dimension,number of junction voxels,and longest shortest path,achieved an area under the curve of 0.753(95%CI:0.622-0.873).Calibration curves confirmed a high agreement between predicted and actual outcomes,and DCA validated the model's clinical utility.CONCLUSION The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy,enhancing personalized treatment planning.

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

The Effects of Naoxintong Capsule on the Vascular Endothelial Function and Inflammatory Factors in Spontaneously Hypertensive Rats

Objective:To investigate the effects of Naoxintong(NXT)capsule on vascular endothelial function and inflammatory mechanism in spontaneously hypertensive rats.Methods:A total of 100 spontaneously hypertensive rats were divided into model group,positive control group,NXT low-dose group,NXT medium-dose group and NXT high-dose group.Rats in the model group were given an equal dose of normal saline once a day;the positive control group was given telmisartan 50 mg/(kg·d)once a day;the low,middle and high dose groups were given the NTX 0.5,1.0,2.0 mg/(kg·d)once a day,respectively.Rats in each group were continuously intragastrically administered for 12 weeks.The vascular endothelial function index,inflammation index and blood pressure of each group were observed at the end of 8 weeks.Results:Endothelin(ET),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)and systolic blood pressure levels were lower in the positive control group and NXT group compared with model group.In the model group,the NO level was lower than the positive control group and NXT group;the levels of ET,IL-6,TNF-α,CRP and systolic blood pressure in the middle-dose group and the high-dose group were lower than those in the positive control group and NXT low-dose group.Furthermore,the level of NO was higher in positive control group and NXT middle and high dose group compared with model group.The levels of ET,IL-6,TNF-α,CRP and systolic pressure in NXT high dose group were lower than in NXT middle dose group,while the level of NO was higher in NXT high group than in NXT middle dose group and the difference was statistically significant(p<0.05).Conclusions:NXT has obviously antihypertensive effect on spontaneously hypertensive rats,and its mechanism may be related to the improvement of vascular endothelial function and inflammatory factors.

Hippocampal CA1 pyramidal cells and neurotrophic factors in a rat model of vascular dementia following Xiongma drop pill versus Ginkgo leaf tablets

BACKGROUND： Previous studies have demonstrated the neuroprotective effects of Xiongma drop pill （XMDP） in a mouse model of vascular dementia. Neurotrophic factors play an important role in repair and regeneration of injured neurons. OBJECTIVE： To compare the effects of XMDP and Ginkgo leaf tablets on the appearance and number of hippocampal CA1 pyramidal neurons, as well as neurotrophic factor content in brain tissues, during vascular dementia formation to explore the neuroprotective mechanisms of XMDP. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Pharmacology, College of Pharmacy, Harbin University of Commerce between April 2007 and December 2008. MATERIALS： XMDP was prepared by the College of Pharmacy, Harbin University of Commerce, with each 40 mg pill containing ferulic acid （≥ 0.149 mg） and gastrodin （≥ 0.171 mg）. Ginkgo leaf tablets were purchased from Taiyuan Qianyuan Pharmacy, China. METHODS： Healthy, adult, male, Wistar rats were randomly assigned to 6 groups： sham-operation, model, XMDP （high-, middle-, and low- dose）, and Ginkgo leaf tablets. The 6 groups were subdivided into two subgroups according to administration days, i.e., 30 and 60 days, with 8 animals in each subgroup. Rats in the model, XMDP, and Ginkgo leaf tablets groups were subjected to permanent bilateral ligation of the common carotid artery to establish a vascular dementia model. At 8 days after model establishment, all groups received intragastric administration once daily of the following： 10 mL/kg normal saline in the sham-operation and model groups; 0.4, 0.2, and 0.1 g/kg XMDP in the high-, middle-, and low-dose XMDP groups, respectively; and 50 mg/kg Ginkgo leaf tablets in the Ginkgo leaf tablets group. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe appearance and to quantify the number of hippocampal CA1 pyramidal neurons. Brain-derived neurotrophic factor and nerve growth factor concentrations in brain tissues were detected by enzyme-linked immunosorbent assay. RESULTS： Following model establishment, hippocampal CA1 neurons exhibited pathological changes. Compared with the sham-operation group, the number of pyramidal neurons significantly decreased （P 〈 0.05 or P 〈 0.01）, and neurotrophic factor concentration increased in the model rats （P 〈 0.05 or P 〈 0.01）. XMDP attenuated neuronal injury in a dose-dependent manner： the number of pyramidal neurons and neurotrophic factor concentrations were significantly increased compared with the model group （P〈 0.05 or P〈 0.01）. High- and middle-dose XMDP resulted in equivalent effects to Ginkgo leaf tablets. In addition, neurotrophic factor concentrations in all XMDP groups, after 60 days of administration, were remarkably greater than corresponding concentrations at 30 days （P 〈 0.05 or P 〈 0.01 ）. CONCLUSION： Hippocampal CA1 pyramidal cells exhibited pathological injury following establishment of the vascular dementia model. Middle- and high-dose XMDP increased neurotrophic factor expression in the brain of vascular dementia rats, which suggested neuroprotection equivalent to Ginkgo leaf tablets.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.