Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease.

Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium of gastric mucosa in patients with nodular gastritis

AIM:The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT).Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center,strongly associated with H pylori infection.The purpose of this study was to address the implication of the MAdCAM-1/integrin β7 pathway in NG. METHODS:We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls.A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM- 1 and integrin β7.In simultaneous viewing of serial sections, the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated.We also performed immunostaining with anti-CD20,CD4,CD8 and CD68 antibodies to determine the lymphocyte subsets co- expressing integrin β7. RESULTS:Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection.Of note,the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls.Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates.Integrin β7-expressing mononuclear cells,mainly composed of CD20 and CD4 lymphocytes,were associated with vessels lined with MAdCAM-1-expressing endothelium.CONCLUSION: Our results suggest that the MAdCAM一1/ integrin a4p7 homing system may participate in gastric inflammation in response to H py/o}i-infection and contributes to MALT formation, typically leading to the development of NG.

The Role of Endoplasmic Reticulum Stress-related Apoptosis in Vascular Endothelium Pathogenesis

Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.

Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)injury of isolated cerebral basilar artery(BA)and erebral ischemia reperfusion(CIR)injury in rat models.In isolated rat BA rings,HR causes endothelial dysfunction(ED)and acetylcholine(ACh)induces endothelium-dependent vasodilation.The myography result showed that SCU(100μM)was able to significantly improve the endothelium-dependent vasodilation induced by Ach.However,SCU did not affect the ACh-induced relaxation in normal BA.Further studies suggested that SCU(10-1000μM)dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase(PKG)inhibitor Rp-8-Br-cGMPs(PKGI-rp,4μM).Pre-incubation with SCU(500μM)reversed the impairment of endothelium-dependent vasodilation induced by HR,but the reversing effect was blocked if PKGI-rp(4μM)was added.The brain slice staining test in rats’model of middle cerebral artery occlusion(MCAO)induced CIR proved that the administration of SCU(45,90 mg/kg,iv)significantly reduced the area of cerebral infarction.The Western blot assay result showed that SCU(45 mg/kg,iv)increased brain PKG activity and PKG protein level after CIR surgery.In conclusion,our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.

Effects of PAF and PAF antagonist WEB 2170 on relaxation of vascular endothelium after brief deoxygenation and reoxygenation

By means of the tension determination of rat thoracic aortic ring. it was found that PAF depressed the acetylcholine (Ach)-induced relaxation of the rings, having undergone 20 min of deoxygenation followed by 30 min of reoxygenation, to 36. 1% of norepinephine(NE) precontraction. PAF receptor antagonist WEB 2170 markedly improved the Ach-induced relaxation of the brief deoxygenated and reoxygenated rings to 86. 7 % of NE precontraction. The results indicated that PAF may be one of the mediators involved in the endothelium relaxation dysfunction related to brief deoxygenation and reoxygenation, and that PAF antagonist WEB 2170 has the protective effect on endothelium relaxation function.

Clinical effect of Calcium Dobesilate combinated with Alprostadil in the vascular endothelium of patients with diabetic nephropathy

Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and record the untoward effect. Method: A totoal of 120 patients with DN, then they were randomly divided into control group (n=60) and observation group(n=60). Two groups were given hypoglycemic (melbinum)+improving circulatory (calcium dobesilate), and observation group were given alprostadil on the basic, they were treated 30 days. After treatment, we observed the changes of fasting plasma glucose (FBG), 2-hour postprandial blood glucose (2hPBG), the factot of vasomotion angiokinesis (nitrogen oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)), diastolic function of vascular endothelium (flow mediated dilation (FMD), nitroglycerin mediated dilation (NMD)), renal function index (glomerular filtration rate (GFR), creatinine (Cr), blood urea nitrogen (BUN), albumin excrete rate (AER), urinary albumin creatinine ratio (UACR), urinary albumin evacuate ratio (UAER)), and record the untoward effect. Results: After treatment, the FBG, 2hPBG were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the FBG, 2hPBG in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the ET-1, VEGF were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the ET-1, VEGF in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the NO, FDM, NDM were higher than before treatment in both groups, the difference had statistical significance (P<0.05), and the NO, FDM, NDM in the observation group were higher than the control group, and the difference had statistical significance (P<0.05). After treatment, the GFR, Cr, BUN, AER, UACR, and UAER were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the GFR, Cr, BUN, UACR, and UAER in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). Conclusions: Treatment of the patients with DN before improving the cardiovascular system and hypoglycemic, giving the alprostadil can improve the function of vascular endothelium, rasing the clinical effect and safety.

Effects of α-lipoic acid on oxidative stress, vascular endothelium function and renal function in patients with diabetic nephropathy

Objective:To investigate the effects ofα-lipoic acid on oxidative stress, vascular endothelium function and renal function in diabetic nephropathy patients.Methods: According to random data table method, a total of 80 patients with diabetic nephropathy from September 2016 to August 2017 were divided into observation group and control group (n=40). The patients of control group were treated with routine therapy while the patients of observation group were given intravenous infusion ofα-lipoic acid on the basis of conventional therapy. The levels of oxidative stress, vascular endothelium function and renal function changes were compared between the two groups before and after the treatment.Results:The levels of SOD, MDA, NO, ET-1, RBP and CysC in the two groups before treatment were not statistically significant. Compared with the levels before treatment, the level of SOD in the observation group was significantly increased and the level of MDA was significantly decreased;the level of SOD in the observation group was significantly higher than that in the control group, and the level of MDA was significantly lower than that of the control group;the above differences were statistically significant. The levels of SOD and MDA had no significant changes in the control group before and after treatment. After treatment, the levels of ET-1, RBP and CysC in the two groups were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of NO in the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group was significantly higher than that of the control group;the above differences were statistically significant.Conclusions: On the basis of conventional treatment, combining withα-lipoic acid can better reduce the level of oxidative stress, improve vascular endothelial function, renal function in patients with diabetic nephropathy, which has an important clinical value.

Effect of Huangqi Xiaoke Recipe combined with alprostadil on qi and yin deficiency type diabetic nephropathy and its effect on vascular endothelium and oxidative stress

Objective: To observe the clinical efficacy of Huangqi Xiaoke Decoction combined with alprostadil on qi and yin deficiency type diabetic nephropathy (DN) and its effect on vascular endothelium and oxidative stress. Methods: A total of 72 patients with qi and yin deficiency type DN who were admitted to the diabetes specialist ward and outpatient department of Baoan District Hospital of Shenzhen from January 2017 to July 2018 were enrolled. The patients were divided into the control group and the observation group according to the random number method. 36 cases in each group. Both groups were treated with conventional treatments such as hypoglycemic, hypotensive, lipid-lowering and anti-platelet aggregation. The control group was treated with alprostadil on the basis of conventional treatment. The observation group was given orally on the basis of the control group. Both groups were treated once a day for a total of 4 weeks. Compare the clinical syndrome scores and clinical efficacy of the two groups before and after treatment;fasting blood glucose (FPG), glycosylated hemoglobin (HbA1C), blood lipids (TC, TG, LDL, HDL), serum creatinine (SCr), blood urea nitrogen (BUN Endothelin-1 (ET-1), nitric oxide (NO), von Willebrand factor (vWF);glutathione peroxidase (GSH-Px), superoxide disproportionation The level of enzyme (SOD), malondialdehyde (MDA). Results:The total effective rate of TCM syndromes in observation group was 94.44%, which was significantly different from 72.22% in the control group. The scores of TCM syndromes in the observation group were significantly lower than those in the control group;Compared with the control group, the HDL-C of the observation group did not change much, there was no statistical difference;FBG, HbA1C, SCr, BUN, TC, TG, LDL-C, ET-1, vWF, MDA Significantly decreased, NO, GSH-Px, SOD increased significantly, with significant difference. Conclusion: Huangqi Xiaoke Decoction combined with alprostadil in the treatment of qi and yin deficiency type DN has significant curative effect, which can not only lower blood sugar, regulate blood lipids, improve renal function and clinical symptoms, but also inhibit oxidative stress and protect endothelial function.

Zinc(Ⅱ)metal-organic framework eluting titanium implant as propulsive agent to boost the endothelium regeneration

The advent of antiproliferative drug-eluting vascular stents can dramatically reduce in-stent restenosis via inhibiting the hyperproliferation of vascular smooth muscle cells.However,the antiproliferative drugs also restrain the repair of the injured endothelial layer,which in turn leads to the very later in-stent restenosis.Evidence points that competent endothelium plays a critical role in guaranteeing the long-term patency via maintaining vascular homeostasis.Boosting the regeneration of endothelium on the implanted vascular stents could be rendered as a promising strategy to reduce stent implantation complications.In this regard,bioactive zinc(II)metal-organic framework modified with endothelial cell-targeting Arg-Glu-Asp-Val peptide was embedded in poly(lactide-co-caprolactone)to serve as a functional coating on the surface of titanium substrate,which can promote the proliferation and migration of endothelial cells.The in vitro cell experiments revealed that the zinc(II)metal-organic framework embedded in the polymer coating was able to modulate the behaviors of endothelial cells owing to the bioactive effects of zinc ion and peptide.Our results confirmed that zinc(II)metal-organic framework eluting coating represented a new possibility for promoting the repair of the damaged endothelium with potential clinical implications in vascular-related biomaterials and tissue engineering applications.

LUPUS NEPHRITIS COMPLICATED WITH MALIGNANT HYPERTENSION:FROM RENAL VASCULAR PATHOLOGY TO CLINICAL RELEVANCE

Objective To investigate the clinical and pathological characteristics of lupus nephritis patients complicated with malignant hypertension.Methods We retrospectively studied 19 patients with lupus nephritis complicated with malignant hypertension who underwent renal biopsy between January 2002 and December 2006.Results Of 19 patients,3 were men and 16 were women,with a mean age of 24.4±7.7 years old.All had positive antinuclear antibodies and low serum complement was found in 13 patients.All were anemic and 12 of them were thrombocytopenic.Impaired renal function was found in 17 patients with an average serum creatinine of 184.5±88.9 μmol/L.Severe intrarenal arteriolar lesion was found in all patients.Six patients had lupus vasculopathy,11 patients had renal thrombotic microangiopathy lesion,2 had severe arteriosclerosis.All patients received steroids and immunosuppressive drugs,15 received angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)with resultant well-controlled blood pressure.Thrombocytopenia and hemolytic anemia resolved remarkably.The renal function improved or recovered in 14 of 17 patients,and 3 developed end-stage renal disease on maintenance dialysis.Conclusions Severe intrarenal vascular lesion complicated with renal nephritis parallels clinical manifestation of malignant hypertension.Renal pathology is the key of treatment strategy emphasizing on the significance of renal vascular involvement and type.On the basis of immunosuppressive drugs and steroids to control systemic lupus activity,timely initiation of ACEI/ARB could be of benefit to blood pressure control and long term renal survival.

Choroidal neovascularization secondary to pathological myopia

Myopic choroidal neovascularization(m CNV), one of the complications of pathological myopia, is also one of the leading causes of visual impairment worldwide. The socioeconomic impact of mC NV in Asian countries is particularly significant due to the rising incidence of pathological myopia. There have been major advances in the treatment of mC NV in the past few years. Previous treatment modalities, such as thermal laser photocoagulation and photodynamic therapy, aimed to prevent vision loss;however, newer modalities such as intravitreal anti-vascular endothelial growth factor(VEGF) agents have been shown to successfully restore vision in many patients. Challenges remain as long term safety and efficacy of anti-VEGF agents are unknown. This article aims to provide a review of the literature of the epidemiology, progression, clinical course and treatment modalities as well as areas of future developments related to myopic CNV.

Whole mount of adult ear skin as a model to study vascular malformations

Background:Genetic analysis in human patients has linked mutations in PIK3CA,the catalytic subunit of PI-3′Kinase,to sporadic incidences of vascular malformations.Methods:We have developed a mouse model with inducible and endothelial-specific expression of PIK3CA H1047R,resulting in the development of vascular malformations.Systemic induction of this mutation in adult mice results in rapid lethality,limiting our ability to track and study these lesions;therefore,we developed a topical and local induction protocol using the active metabolite of tamoxifen,4OH-T,on the ear skin of adults.Results:This approach allows us to successfully model the human disease in a mature and established vascular bed and track the development of vascular malformations.To validate the utility of this model,we applied a topical rapamycin ointment,as rapamycin is therapeutically beneficial to patients in clinical trials.We found that the induced ear lesions showed significant attenuation after treatment,which was easily quantified.Conclusions:These data collectively provide evidence of a new model to study vascular malformations in adult tissues,which should be particularly useful in environments lacking specialized small-animal imaging facilities.

Hydroxysafflor Yellow A Promotes Vascular Endothelial Cell Proliferation via VEGF/VEGF Receptor

Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.

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。

非布司他联合阿托伐他汀钙治疗高脂血症合并高尿酸血症患者的效果

目的:观察非布司他联合阿托伐他汀钙治疗高脂血症合并高尿酸血症患者的效果。方法:选取2020年2月至2023年3月该院收治的120例高脂血症合并高尿酸血症患者进行前瞻性研究,按照随机数字表法将其分为对照组和观察组各60例。对照组予以阿托伐他汀钙治疗,观察组在对照组基础上联合非布司他治疗。比较两组临床疗效、治疗前后血脂指标[总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]水平、血尿酸水平、血管内皮功能指标[可溶性细胞间黏附分子-1(sICAM-1)、内皮素-1(ET-1)]水平和不良反应发生率。结果:观察组治疗总有效率为93.33%(56/60),高于对照组的80.00%(48/60),差异有统计学意义(P<0.05);治疗后,观察组TG、TC、LDL-C、血尿酸水平均低于对照组,HDL-C水平高于对照组,差异有统计学意义(P<0.05);观察组sICAM-1、ET-1水平均低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:非布司他联合阿托伐他汀钙治疗高脂血症合并高尿酸血症患者可提高治疗总有效率,改善血脂指标水平,降低血尿酸和血管内皮功能指标水平,效果优于单纯阿托伐他汀钙治疗。

补阳还五汤干预急性心肌梗死疾病机制的研究进展

急性心肌梗死(AMI)是一种急性发作的冠脉综合征,已成为严重影响人类生活健康的重大疾病,中医药对AMI具有较好的治疗效果,近年来补阳还五汤干预AMI的作用成为了研究的热点。现代药理学研究表示补阳还五汤具有抗血栓、保护血管、抗炎症和抑制细胞凋亡的作用,补阳还五汤具有多靶点,多通路全方位治疗的优点。从保护血管内皮、促进血管生成、抑制心肌重构、抑制炎症因子、抑制细胞凋亡等方面对补阳还五汤干预AMI的研究进展进行综述,为AMI的中医药诊疗研究提供文献依据。

乳腺癌组织内VEGF-C、HIF-1α表达与血管生成的相关性研究

目的:探讨乳腺癌患者组织内血管内皮生长因子-C(VEGF-C)、缺氧诱导因子-1α(HIF-1α)表达与血管生成的关系。方法:选取2022年1月—2023年12月泰安市中心医院收治的198例乳腺癌女性患者,并选取同期经病理学检查为乳腺纤维瘤患者50例为对照。采用免疫组化S-P法检测乳腺癌和乳腺纤维瘤组织中VEGF-C、HIF-1α表达及微血管密度(MVD)数,分析VEGF-C、HIF-1α表达与临床病理特征及MVD的关系。结果:乳腺癌患者乳腺组织中VEGF-C、HIF-1α阳性表达率及MVD数均高于乳腺纤维瘤患者,差异有统计学意义(P<0.05)。VEGF-C阳性与阴性表达者年龄、肿瘤直径、组织学分级、ER表达、PR表达等临床病理特征比较,差异无统计学意义(P>0.05);VEGF-C阳性表达者有淋巴结转移、TNM分期为Ⅲ~Ⅳ期、分子分型(Luminal B、HER-2阳性、基底细胞)的患者占比及MVD均高于VEGF-C阴性表达者,差异有统计学意义(P<0.05)。HIF-1α阳性与阴性表达者年龄、肿瘤直径、ER表达、PR表达、分子分型等临床病理特征比较,差异无统计学意义(P>0.05);HIF-1α阳性表达者组织学分级为Ⅱ级、Ⅲ级、有淋巴结转移、TNM分期为Ⅲ~Ⅳ期的患者占比及MVD均高于HIF-1α阴性表达者,差异有统计学意义(P<0.05)。结论:乳腺癌患者组织内VEGF-C、HIF-1α阳性表达率明显升高,并且还与肿瘤血管生成存在显著相关性。

PTEN、CA125、sVEGFR1、NGAL在子宫内膜癌患者血清中的表达及与病理特征的关系

目的 探讨第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)、糖类抗原125(CA125)、可溶性血管内皮生长因子受体-1(sVEGFR1)、中性粒细胞明胶酶相关脂质载运蛋白(NGAL)在子宫内膜癌(EC)患者血清中的表达及与病理特征的关系。方法 选取2019年1月至2021年6月于在邯郸市第一医院行全子宫切除术并经病理诊断的120例EC患者为研究组,选择同期80例良性病变子宫内膜患者为对照组,用酶联免疫吸附法检测并比较2组患者血清PTEN、CA125、sVEGFR1、NGAL水平,收集2组临床病理资料,分析血清PTEN、CA125、sVEGFR1、NGAL与研究组患者病理特征的关系。结果 研究组血清CA125、NGAL水平高于对照组,血清PTEN、sVEGFR1水平低于对照组(P<0.05)。分化程度越低血清CA125、NGAL水平越高,血清PTEN、sVEGFR1水平越低(P<0.05);临床分期Ⅲ~Ⅳ期患者血清PTEN高于Ⅰ~Ⅱ期(P<0.05);临床分期Ⅲ~Ⅳ期、有淋巴结转移、浸润深度≥50%患者血清CA125、NGAL水平升高,血清sVEGFR1水平降低(P<0.05)。血清PTEN与临床分期呈负相关,与分化程度呈正相关(P<0.05);血清CA125、NGAL与临床分期、淋巴结转移、浸润深度呈正相关,与分化程度呈负相关(P<0.05);血清sVEGFR1与临床分期、淋巴结转移、浸润深度呈负相关,与分化程度呈正相关(P<0.05)。结论 CA125、NGAL在EC患者血清中呈高表达,PTEN、sVEGFR1呈低表达,均与EC患者病理特征有一定相关性,可作为EC早期诊断与疾病进展的潜在生物学标志物。

m6A甲基化修饰非编码RNA调控病理性心脏重塑的作用

背景:m6A甲基化修饰非编码RNA是病理性心脏重塑形成机制的研究热点,在心血管疾病的发生发展中起着重要作用。目的:总结m6A甲基化修饰非编码RNA对调控病理性心肌肥大、心肌细胞死亡、心肌纤维化与血管重塑等病理性心脏重塑主要过程的可能作用机制。方法:以“m6A甲基化修饰,非编码RNA,病理性心肌肥大,心肌细胞凋亡,心肌细胞焦亡,心肌细胞铁死亡,心肌纤维化,血管重塑”为中文主题词,以“m6A、non-coding RNA,pathological cardiac hypertrophy,cardiomyocyte apoptosis,cardiomyocyte pyroptosis,cardiomyocyte ferroptosis,myocardial fibrosis,vascular remodeling”为英文主题词,检索中国知网、PubMed、Web of Science数据库1974年1月至2023年4月发表的相关文献,对符合筛选标准的86篇文献进行综述。结果与结论:①m6A甲基化修饰是一种动态可逆的表观遗传修饰方式;②病理性心脏重塑主要包括病理性心肌肥大、心肌细胞死亡、心肌纤维化、血管重塑,m6A相关酶可调控病理性心脏重塑相关进程;③m6A甲基化修饰相关酶可通过多种非编码RNA与不同信号通路参与调控病理性心脏重塑过程,可作为心血管疾病新的潜在干预方式;④在病理性心脏重塑中,m6A甲基化修饰与非编码RNA之间的调控关系仍处于起步阶段,随着表观遗传学的发展,m6A甲基化修饰非编码RNA来调控病理性心脏重塑有望有新的发展。

Expression of vascular endothelial growth factor and its role in oncogenesis of human gastric carcinoma

AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.