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.

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).

Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke

Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

Serum vascular endothelial growth factor and cortisol expression to predict prognosis of patients with hypertensive cerebral hemorrhage

BACKGROUND Cerebral hemorrhage is a common and severe complication of hypertension in middle-aged and elderly men.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and cortisol(Cor)and the prognosis of patients with hypertensive cerebral hemorrhage.METHODS A hundred patients with hypertensive intracerebral hemorrhage were enrolled from January 2020 to December 2022 and assigned to the hypertensive intracerebral hemorrhage group.Another 100 healthy people who were examined at our hospital during the same period were selected and assigned to the healthy group.Peripheral venous blood was collected,and serum Cor and VGEF levels were measured through enzyme linked immunosorbent assay.RESULTS A statistically significant difference in serum Cor and VGEF levels was observed among patients with varying degrees of neurological impairment(P<0.05).Serum Cor and VGEF levels were significantly higher in the severe group than in the mild-to-moderate group.Cor and VEGF levels were significantly higher in patients with poor prognoses than in those with good prognoses.Multiple logistic regression analysis revealed that serum Cor and VGEF levels were independent factors affecting hypertensive intracerebral hemorrhage(P<0.05).CONCLUSION Cor and VGEF are associated with the occurrence and development of hypertensive cerebral hemorrhage and are significantly associated with neurological impairment and prognosis of patients.

Vascular endothelial growth factor protein and gene delivery by novel nanomaterials for promoting liver regeneration after partial hepatectomy

Partial hepatectomy(PH)can lead to severe complications,including liver failure,due to the low regenerative capacity of the remaining liver,especially after extensive hepatectomy.Liver sinusoidal endothelial cells(LSECs),whose proliferation occurs more slowly and later than hepatocytes after PH,compose the lining of the hepatic sinusoids,which are the smallest blood vessels in the liver.Vascular endothelial growth factor(VEGF),secreted by hepatocytes,promotes LSEC proliferation.Supplementation of exogenous VEGF after hepatectomy also increases the number of LSECs in the remaining liver,thus promoting the reestablishment of the hepatic sinusoids and accelerating liver regeneration.At present,some shortcomings exist in the methods of supplementing exogenous VEGF,such as a low drug concentration in the liver and the reaching of other organs.Moreover,VEGF should be administered multiple times and in large doses because of its short half-life.This review summarized the most recent findings on liver regeneration and new strategies for the localized delivery VEGF in the liver.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion

BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

Efficacy and safety of anti-vascular endothelial growth factor agents on corneal neovascularization: A meta-analysis

BACKGROUND Corneal neovascularization(CoNV)is the second major cause of blindness.Vascular endothelial growth factor(VEGF)inhibitors,e.g.,bevacizumab,have been used to prevent CoNV.AIM We conducted an updated systematic review and meta-analysis of clinical trials to examine the efficacy and safety of anti-VEGF in CoNV.METHODS A literature search was conducted using three electronic databases.Mean difference(MD),standard mean difference(SMD),and relative risk(RR)are used to estimate the effect size.RESULTS Nine randomized controlled and three non-randomized trials were obtained.The pooled results demonstrated a significant reduction of CoNV area/Length(SMD=-1.17,95%CI:-1.58 to-0.75),best corrected visual acuity(MD=-0.54,95%CI:-0.91 to-0.17),and graft rejection(RR=0.44,95%CI:0.24 to 0.8)and failure(RR=0.39,95%CI:0.19 to 0.78)rates in the anti-VEGF group than the placebo group.A non-significant reduction of the epithelial defect was also observed in the bevacizumab group compared with the placebo(RR=0.56,95%CI:0.30 to 1.06).Compared with a placebo,the unsynthesizable trials also support that bevacizumab improves visual acuity,CoNV,graft rejection,and failure rates.Trials reporting other comparisons revealed the superiority of combined remedy with bevacizumab compared to other treatments in reducing CoNV.CONCLUSION Anti-VEGF agents,mainly bevacizumab,are an effective and safe treatment for CoNV of all causes and prevent corneal graft rejection and failure in corneal transplantation.

Role of vascular endothelial growth factor B in nonalcoholic fatty liver disease and its potential value

Nonalcoholic fatty liver disease(NAFLD)refers to fatty liver disease caused by liver injury factors other than alcohol.The disease is characterized by diffuse fat infiltration,including simple steatosis(no inflammatory fat deposition),nonalcoholic fatty hepatitis,liver fibrosis,and so on,which may cause liver cirrhosis,liver failure,and even liver cancer in the later stage of disease progression.At present,the pathogenesis of NAFLD is still being studied.The"two-hit"theory,represented by lipid metabolism disorder and inflammatory reactions,is gradually enriched by the"multiple-hit"theory,which includes multiple factors,such as insulin resistance and adipocyte dysfunction.In recent years,vascular endothelial growth factor B(VEGFB)has been reported to have the potential to regulate lipid metabolism and is expected to become a novel target for ameliorating metabolic diseases,such as obesity and type 2 diabetes.This review summarizes the regulatory role of VEGFB in the onset and development of NAFLD and illustrates its underlying molecular mechanism.In conclusion,the signaling pathway mediated by VEGFB in the liver may provide an innovative approach to the diagnosis and treatment of NAFLD.

Safety and efficacy of intravitreal anti vascular endothelial growth factor for severe posterior retinopathy of prematurity with flat fibrovascular proliferation

BACKGROUND Intravitreal anti-vascular endothelial growth factor(IVA)injection is known to cause contraction of fibrovascular proliferation(FVP),when present in severe retinopathy of prematurity(ROP).AIM To assess the structural outcomes of IVA injection in the treatment of severe posterior ROP with significant FVP.METHODS It was a retrospective study in which 36 eyes of 18 preterm babies who developed>4 clock hours of FVP in zone I or posterior zone II,were treated with either intravitreal 0.625 mg bevacizumab or intravitreal 0.2 mg of ranibizumab.Favorable structural outcome included resolution of plus disease and FVP without the development of tractional retinal detachment.Secondary outcome measure included either full retinal maturation at follow-up or development of recurrent disease requiring additional treatment.Adverse outcomes included progression to retinal detachment.RESULTS The mean gestational age of the 18 preterm babies was 30 wk(range 27-36),and mean birth weight was 1319 g(range 650-1980 g).Mean post-menstrual age(PMA)at the time of primary treatment was 35.5 wk(range 31-41 wk).All eyes showed regression of plus disease and FVP.5 eyes of 3 babies showed reactivation of disease and were treated with repeat IVA(n=2 eyes)or peripheral laser photocoagulation(n=3 eyes)respectively.16 out of 36(44%)reached retinal vascular maturation at final follow up at 5 years.CONCLUSION There was good resolution of severe posterior ROP with FVP with IVA,with retinal maturity of 44%at 5 year follow-up and a reactivation rate of 13.8%.When the IVA injection is given prior to 37 wk PMA,while disease is in phase 2,it is less likely to cause contracture of pre-existing FVP.

Abnormal expression of vascular endothelial growth factor (VEGF) and its clinical features in tissues of human lung cancer

Objective： Angiogennesis, the formation of new blood vessels from the existing vascular bed, is essential step for growth and invasion of primary rumor. Vascular endothelial growth factor （VEGF） is known to play crucial role in tumor angiogenesis. In the present study, we investigate the expression of VEGF and VEGF-mRNA in the angiogennesis, metastasis and prognosis of lung cancer. Methods： The VEGF cellular distributions and expression in 38 specimens of patients with lung cancer were investigated with immunohistochemistry stain technology. The total RNAs in 38 tissues of lung cancer was measured, then the levels of VEGF-mRNA expression were analyzed by a reverse-transcription polymerase chain reaction （RT-PCR） assay. The levels of VEGF in sera of patients with lung cancer, benign lung diseases and healthy controls were detected through Enzyme linked immunosorbent assay （ELISA） method. Results： The VEGF positive stain was 76% in 38 cases of lung cancer specimens. The 89% rate of VEGF stain was found for clinical stage Ⅲ cases and 92% for stage Ⅳ lung cancers. The significantly higher expression of VEGF was evidenced in patients with lymph node metastasis （84%）, distant metastasis （90%）, and lung cancers with lower histological differentiation （89%）, respectively. The expression level of total RNA was significantly higher in patients with lung cancers than that in their paracancerons or distant lung tissues. The VEGF expressions were tightly correlated with total RNA concentration of lung carcinoma （ P 〈 0.01 ）. The predominant expressions of VEGF121 and VEGF165 gene fragments were found in lung cancer specimens by RT-PCR analysis. No significant difference of serum VEGF levels was detected between cases with lung cancer and patients with benign diseases. However, the VEGF level of cases with benign diseases was decreased significantly after patients with anti-inflammation medication. Conclusion： The present data suggested that the rumor tissue VEGF expression and VEGF-mRNA analysis in patients with lung cancer be a useful indicator for angiogenesis and metastasis of lung cancer.

Expression of vascular endothelial growth factor and its receptors VEGFR-1 and 2 in gastrointestinal stromal tumors,leiomyomas and schwannomas

AIM: To investigate the role of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal stromal tumors (GISTs). METHODS: Thirty-three GISTs, 15 leiomyomas and 6 schwannomas were examined by immunohistochemistry in this study. RESULTS: VEGF protein was expressed in the cytoplasm of tumor cells, and VEGFR-1 and 2 were expressed both in the cytoplasm and on the membrane of all tumors. Immunohistochemical staining revealed that 26 GISTs (78.8%), 9 leiomyomas (60.0%) and 3 schwannomas (50.0%) were positive for VEGF; 24 GISTs (72.7%), 12 leiomyomas (80.0%) and 4 schwannomas (66.7%) were positive for VEGFR-1; 30 GISTs (90.9%), 5 leiomyomas (33.3%) and 4 schwannomas (66.7%) were positive for VEGFR-2. VEGFR-2 expression was statistically different between GISTs and leiomyomas (p < 0.0001). However, there was no correlation between the expression of VEGF pathway componenets and the clinical risk categories. CONCLUSION: Our results suggest that the VEGF pathway may play an important role in the differentiation of GISTs, leiomyomas and schwannomas.

Downregulation of transforming growth factor-<i>β</i>(TGF-<i>β</i>) and vascular endothelial growth factor (VEGF) in ehrlich ascites carcinoma-bearing mice using stearic acid-grafted carboxymethyl chitosan (SA-CMC)

The present study was conducted to investigate the use of stearic acid-grafted carboxymethyl chitosan(SA-CMC) as a downregulator for trans- forming growth factor-β (TGF- β) and vascular endothelial growth factor (VEGF) in Ehrlich ascites carcinoma (EAC)-bearing mice. The antitumor effect of stearic acid-grafted carboxymethyl chitosan was assessed by the estimation of TGF- β and VEGF in serum in addition to the estimation of tumor volume, median survival time (MST), percentage of increase in life span (ILS%) as well as the contents of total lipid, DNA and RNA in liver tissues. Hematological profiles (hemoglobin, red blood cells, and platelets) were also assessed. In addition, liver function tests and the redox status were estimated. TGF- β, VEGF, DNA, RNA, and malondialdehyde (MDA) levels, in addition to serum alanine transaminase (ALT) and gamma glutamyl transferase (GGT) activities as well as total white blood cells counts and tumor volume were all highly significantly increased (P < 0.001) in untreated EAC-bearing mice compared to controls. However, hematological profiles, total lipid in liver tissues and serum albumin were highly decreased in EAC-bearing mice compared to controls. All these parameters were restored to the normal levels in SA-CMC treated EAC-bearing mice com- pared to the untreated EAC-bearing mice. It is thus concluded that stearic acid-grafted carboxymethyl chitosan has a remarkable antitumor activity against EAC in Swiss albino mice through downregulation of TGF-β and VEGF.

Expression of Vascular Endothelial Growth Factor (VEGF) in Human Osteosarcoma Cells Transfected with Adeno-associated Virus-antisense VEGF

Summary: The expression of protein vascular endothelial growth factor (VEGF) in osteosarcoma cells transfected with adeno-associated virus (rAAV)-antisense VEGF was studied to provide the foundation of osteosarcoma treatment through antivascularization. The rAAV-antisense VEGF at different doses (0, 20, 50, 100, 200, 240 μl) was transfected into osteosarcoma MG-63 cell. The cells and culture supernatants were collected before and after tansfection. The expression of VEGF protein was detected by using immunohistochemical staining (SP) and Western blot. SP and Western-blot tests revealed that the MG-63 Cells transfected with rAAV-antisense VEGF had less staining than those without transfection with rAAV-antisense VEGF, and the staining intensity was negatively correlated with the doses of genes. The corresponding A values of transfected genes with different doses of rAAV-antisense VEGF (0, 20, 50, 100, 200, 240 μl) were 86 614±13 776, 73 245±15 414, 61 078±12 124, 54 657±10 953, 39 802±11 308, 32 014±15 057 respectively, with the difference being significant (P<0.05). It was concluded that the expression of VEGF protein in MG-63 cells could be inhibited by rAAV-antisense VEGF.

THE EXPRESSIONS AND SIGNIFICANCES OF p15,p16 AND VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) IN GASTRIC CARCINOMA

To investigate the relationships between the expressions of p15,p16 and vascular endothelial growth factor (VEGF) and gastric carcinoma(GC). Methods: Using Immunohistochemical staining to examine the expressions of p15, p16 and VEGF In archival wax-embedded specimens of 80 GC and 20 gastric benign disease (GBD). Results: The positive expression rate (PER) of p15 was significantly lower in GC than in GBD (43.75% VS. 69.23%, P<0.05). No relationship was found between PER of p15 and clinicopathologic factors. PER of p16 was 20% in GC, 55% in GBD (P<0.01). PER of p16 wasn't significantly different in gross types, histological types, with or without distant metastasis and pTNM stages. PER of p16 was 71.43% in invasive mucosa or submucosa group, 17.24% in invasive muscle group and 13.64% in invasive serosa group (P<0.01); 12.96% in GC with lymph nodes metastasis, 34.62% in GC without lymph node metastasis (P<0.05). PER of VEGF in GC was 75.00%, in GBD 7.69% (P<0.001), in ul-cerative type of GC and infiltrating

Immunohistochemical Evaluation of Vascular Endothelial Growth Factor(VEGF)in Splenic Hemangiomas and Hemangiosarcomas in Dogs

Formation of new blood vessels is paramount for tumour growth and metastatic dissemination and vascular endothelial growth factor (VEGF) is one of the key regulators of this process. The purpose of this study was to evaluate the immunohistochemical expression of VEGF in 23 splenic hemangiosarcomas and 7 splenic hemangiomas in dogs. Blood tests performed previous to splenectomy were analysed for correlation with tumour VEGF expression. Results showed significantly higher VEGF expression in hemangiosarcomas than hemangiomas and lower hematocrit values and red cell count in dogs affected with malignant neoplasia (P < 0.05). These findings suggest the presence of high VEGF levels may be related to the malignant vascular proliferation seen in hemangiosarcomas.

山姜素调节VEGF/SphK1/S1P信号通路对膝骨关节炎大鼠血管生成的影响

目的探讨山姜素(APT)调节血管内皮生长因子/鞘氨醇激酶1/1磷酸鞘氨醇(VEGF/SphK1/S1P)信号通路对膝骨关节炎(KOA)大鼠血管生成的影响。方法采用改良的Videman法构建KOA大鼠模型,将90只大鼠分为对照组(Control组)、模型组(Model组)、山姜素低剂量组(L-APT组)、山姜素高剂量组(H-APT组)、山姜素高剂量组+慢病毒阴性对照组(APT+NC组)、山姜素高剂量组+过表达SphK1慢病毒组(APT+SphK1组),每组15只。HE染色观察大鼠软骨组织病理变化;酶联免疫吸附试验测定软骨组织白细胞介素(IL)-1β、肿瘤坏死因子α(TNF-α)、IL-6、基质金属蛋白酶-13(MMP-13)水平;TUNEL检测软骨组织细胞凋亡情况;免疫组化检测血管内皮生长因子(VEGF)、CD31蛋白表达情况;Western blot检测血管内皮生长因子受体2(VEGFR2)、磷酸化VEGFR2(p-VEGFR2)、SphK1、S1P蛋白水平。结果与Control组比较,Model组大鼠出现病理损伤,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和p-VEGFR2、SphK1、S1P蛋白表达水平增加(P<0.05);与Model组比较,L-APT组、H-APT组病理损伤明显减轻,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和pVEGFR2、SphK1、S1P蛋白表达水平降低(P<0.05);与APT+NC组比较,APT+SphK1组软骨组织病理损伤加重,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和p-VEGFR2、SphK1、S1P蛋白表达水平增加(P<0.05)。结论APT通过抑制VEGF/SphK1/S1P信号通路抑制KOA大鼠血管生成。

益气活血通络方对脊髓型颈椎病模型大鼠miR-126a-5p及VEGF信号通路的影响

目的探讨益气活血通络方对脊髓型颈椎病模型大鼠微小RNA-126a-5p(miR-126a-5p)及血管内皮生长因子(VEGF)信号通路的影响。方法30只健康雄性SD大鼠按照随机数字表法均分为假手术组、模型组和中药组。模型组、中药组均制备脊髓型颈椎病模型。中药组给予益气活血通络方灌胃,假手术组、模型组给予生理盐水灌胃,均为12周。各组干预结束后进行大鼠行为学测试,测定机械性刺激阈值和热刺激回缩时间。处死大鼠,HE染色观察各组椎间盘软骨终板结构的差异。TUNEL染色观察大鼠椎间盘纤维环细胞变化。实时荧光定量聚合酶链式反应检测大鼠椎间盘纤维环组织miR-126a-5p和VEGF mRNA。采用Western blot法检测大鼠椎间盘纤维环组织VEGF蛋白表达。结果与假手术组比较,模型组大鼠椎间盘血管芽数目减少,大鼠椎间盘纤维环细胞破坏明显、大量凋亡且细胞密度降低;模型组和中药组机械性刺激阈值降低,热刺激回缩时间缩短,miR-126a-5p水平降低,VEGF mRNA和蛋白表达水平升高(P<0.05)。与模型组比较,中药组大鼠椎间盘血管芽数目增加,大鼠椎间盘纤维环细胞破坏减轻,大鼠椎间盘纤维环细胞凋亡减少且细胞密度增加,机械性刺激阈值升高,热刺激回缩时间延长,miR-126a-5p水平增加,VEGF mRNA和蛋白表达水平降低(P<0.05)。结论益气活血通络方治疗脊髓型颈椎病的机制可能与上调miR-126a-5p、下调VEGF表达有关。

缺血性视网膜静脉阻塞继发黄斑水肿患者基线血清己糖激酶1抗体滴度与抗VEGF治疗后视力改善的相关性分析

目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗的53例患者,其中缺血性视网膜中央静脉阻塞(CRVO)23例(CRVO组),缺血性视网膜分支静脉阻塞(BRVO)30例(BRVO组)。另选取该院同期30例行超声乳化的白内障患者作为对照组。研究对象行基线血清己糖激酶1抗体滴度检测、眼科常规检查和光学相干断层成像(OCT)检查。所有RVO-ME患者按照“3+按需治疗方案(pro re nata,PRN)”向玻璃体内注射抗VEGF药物治疗。随访12个月,采用多元线性回归分析缺血性RVO-ME患者抗VEGF治疗后视力改善的影响因素。结果CRVO组基线logMAR BCVA高于对照组和BRVO组,CRVO组和BRVO组基线CRT、基线血清己糖激酶1抗体滴度高于对照组,且CRVO组基线CRT、基线血清己糖激酶1抗体滴度高于BRVO组,差异有统计学意义(P<0.05)。RVO-ME患者基线血清己糖激酶1抗体滴度与随访6个月(r=0.377,P=0.005)、9个月(r=0.362,P=0.008)和12个月(r=0.465,P<0.001)时BCVA改善呈正相关,与随访12个月时中断EZ横向长度减少值(r=0.401,P=0.001)呈正相关。多元线性回归分析结果显示,基线logMAR BCVA、基线血清己糖激酶1抗体滴度是缺血性RVO-ME患者抗VEGF治疗随访12个月时BCVA改善的影响因素(P<0.05)。结论己糖激酶1抗体作为一种新的血清生物标志物,与缺血性RVO-ME患者抗VEGF治疗后的视力改善相关。

血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6在结核性胸膜炎胸膜纤维化患者中的变化及临床意义

目的探讨血清和胸腔积液纤溶酶原激活剂抑制物-1(PAI-1)、转化生长因子-β(TGF-β)、血管内皮生长因子(VEGF)、白细胞介素-6(IL-6)在结核性胸膜炎胸膜纤维化患者中的变化及临床意义。方法选取2020年7月至2023年7月该院收治的103例结核性胸膜炎胸膜纤维化患者作为研究对象,治疗2周后,根据糖皮质激素治疗疗效将其分为显效组、非显效组。比较两组治疗前及治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平。采用Spearman相关分析血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平与疗效的相关性。治疗2周后血清PAI-1、TGF-β、VEGF、IL-6水平与胸腔积液中该指标水平之间进行Pearson相关分析。绘制受试者工作特征曲线分析治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平对结核性胸膜炎胸膜纤维化患者疗效的预测价值。结果两组治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平低于治疗前,显效组治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平低于非显效组,差异有统计学意义(P<0.05)。治疗1、2周后血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平与疗效呈负相关(P<0.05)。治疗2周后血清PAI-1、TGF-β、VEGF、IL-6水平和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平呈正相关(r=0.761、0.783、0.812、0.741,均P<0.05)。治疗1、2周后血清和胸腔积液各指标联合检测的曲线下面积(AUC)大于其单独指标的AUC(P<0.05)。结论结核性胸膜炎胸膜纤维化患者血清和胸腔积液PAI-1、TGF-β、VEGF、IL-6水平与疗效有关,血清及胸腔积液PAI-1、TGF-β、VEGF、IL-6联合检测的预测价值较好,能够为临床干预提供参考依据。