星形细胞瘤组织中缺氧诱导因子-1α、VEGF、iNOs的表达及其与MVD的关系

目的 探讨缺氧诱导因子-1α（HIF-1α）与诱生型一氧化氮合酶（iNOs）、血管内皮生长因子（VEGF）在脑星形细胞瘤中的表达以及缺氧与血管形成的生物学意义。方法采用SP免疫组化法,检测HIF-1α、iNOs和VEGF在59例不同病理分级脑星形细胞瘤组织中的表达,CD34标记血管内皮细胞并计数微血管密度（MVD）,分析它们与临床病理参数的关系。结果 ①59例脑星形细胞瘤组织中,HIF-1α、iNOs、VEGF表达的阳性率分别为47．5％（28／59）、71．2％（42／59）和74．6％（44／59）,其中HIF-1α、VEGF与病理分级有统计学意义（P〈0．05）;②HIF-1α、VEGF均与iNOs蛋白表达存在相关性（P〈0．01）;③iNOs、脑肿瘤VEGF与MVD值之间均存在正相关（P〈0．05）。结论 HIF-1α、iNOs、VEGF在脑星形细胞瘤中对缺氧的适应及多血管体系的形成起重要作用;iNOs可能协同HIF-1α上调VEGF的表达。     

食管鳞状细胞癌中HIF-1α、CTSD表达和血管生成拟态的关系及其临床意义

目的观察食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、组织蛋白酶D(cathepsin D,CTSD)的表达情况,分析两者表达与血管生成拟态(vasculogenic mimicry,VM)及ESCC临床病理特征的关系。方法收集120例ESCC组织,采用CD34/PAS套染检测ESCC VM情况;免疫组化En Vision两步法检测ESCC中VM标志性分子血管内皮钙黏素(vascular endothelial cadherin,VE-cadherin)和血管内皮生长因子(vascular endothelial grow factor,VEGF)以及HIF-1α、CTSD的表达,分析HIF-1α和CTSD与ESCC临床病理特征的关系及各指标之间相关性。结果 120例ESCC中HIF-1α和CTSD的表达与患者年龄、性别无关;与淋巴结转移、脉管癌栓形成、临床分期、病理分级等有关;120例ESCC中有25例存在VM;HIF-1α和CTSD在有VM组阳性率明显高于无VM组,且均与VM表达呈正相关;CTSD在HIF-1α阳性组的表达明显高于HIF-1α阴性组,且两者表达呈正相关;VE-cadherin、VEGF在CTSD阳性组的表达率明显高于CTSD阴性组,且与CTSD表达均呈正相关,提示在ESCC中CTSD表达与VM的形成相关。结论 CTSD有可能通过HIF-1α参与ESCC中VM形成过程,另外HIF-1α和CTSD高表达提示ESCC患者预后不良。     

Raptor、Rictor与结直肠癌血管生成的相关性及其临床意义

目的检测Raptor、Rictor与血管生成相关因子HIF-1α、HIF-2α以及VEGF在结直肠癌中的表达,探讨Raptor、Rictor与结直肠癌血管生成的相关性及其临床意义。方法采用免疫组化、Western blot、RT-PCR法检测120例结直肠癌组织及60例正常结直肠黏膜组织中Raptor、Rictor及HIF-1α、HIF-2α、VEGF的表达及其差异;CD34标记微血管密度(microvascular density,MVD);分析各指标间的相关性以及与结直肠癌临床病理特征的关系。结果 Raptor、Rictor、HIF-1α、HIF-2α和VEGF蛋白在结直肠癌中的阳性率均明显高于正常结直肠黏膜组织(P0.05)。Raptor、Rictor在中、低分化结直肠癌中的表达高于高分化结直肠癌(P0.05),同时在淋巴结转移组的表达高于无淋巴结转移组(P0.05);HIF-1α、HIF-2α和VEGF在淋巴结转移组的表达高于无淋巴结转移组(P0.05);Raptor、Rictor阳性的结直肠癌组织中MVD明显高于Raptor、Rictor阴性的结直肠癌组织(P0.05);Raptor与HIF-1α、VEGF在结直肠癌中表达呈正相关(P0.01),Rictor与HIF-2α、VEGF表达呈正相关(P0.01),Raptor与Rictor在结直肠癌中表达呈负相关(P0.01)。结论 m TOR核心分子Raptor、Rictor与结直肠癌的发生、发展及血管生成密切相关,两者以不同途径协同促进结直肠癌的血管生成。     

白芍总苷对子宫内膜异位症大鼠异位组织HIF-1α/VEGF信号通路的影响

目的 探究白芍总苷对子宫内膜异位症（EMs）大鼠缺氧诱导因子1α(HIF-1α)/血管内皮生长因子（VEGF通路的影响。方法 取SD大鼠随机分为假手术组、模型组、白芍总苷组、HIF-1α激动剂（DMOG）组、HIF-1α/VEGF信号通路阻断剂（YC-1）组、白芍总苷+DMOG组，用自体子宫内膜移植法建立EMs模型。各组大鼠持续给药4周后，比较病灶体积，取异位内膜组织，H-E法检测各组子宫内膜组织形态；免疫组化法检测HIF-1α、VEGF、CD34表达；蛋白免疫印迹法（western blot）检测促血管生成素2(Ang-2)、基质金属蛋白酶9(MMP-9)、核转录因子κB(NF-κB)、磷酸化NF-κB(p-NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、前列腺素E2(PGE2)、雌激素受体β(ERβ)、基质环氧酶2(COX-2)、凋亡信号调节激酶1(ASK1)表达水平。结果 与假手术组相比，模型组大鼠异位内膜病灶体积增大，异位内膜组织腺体及间质细胞增多，血管增生严重，HIF-1α介导的血管生成、雌激素分泌相关通路、炎症反应等...     

HIF-1基因RNA干扰对肝癌HepG2细胞VEGF表达的抑制

缺氧诱导因子-1(HIF-1)是细胞缺氧反应网络的关键调节转录因子,而HIF-1α是决定HIF-1活性的亚单位。HIF-1能在缺氧条件下促进血管内皮生长因子(VEGF)依赖性的肿瘤血管形成。本研究构建了针对HIF-1α的pSUPER-EGFP siRNA表达载体,抑制HepG2细胞HIF-1α的表达。RT-PCR和Western blot蛋白印迹检测结果显示,RNA干扰能明显抑制HIF-1α的表达;在缺氧培养条件下,HepG2细胞中VEGF有较高的表达,当HIF-1α基因表达被有效抑制,VEGF mRNA和蛋白质的表达随之大幅下降。本研究结果表明,HIF-1α是血管生成因子VEGF表达的调节因子,通过RNA干扰导致的HIF-1α基因抑制,能下调VEGF的表达,提示HIF-1α基因可作为抗抑制VEGF依赖性的肿瘤血管生成的一个靶点。     

HIF-1α基因RNA干扰对肝癌HepG2细胞VEGF表达的抑制

缺氧诱导因子-1(HIF-1)是细胞缺氧反应网络的关键调节转录因子,而HIF-1α是决定HIF-1 活性的亚单位.HIF-1能在缺氧条件下促进血管内皮生长因子(VEGF) 依赖性的肿瘤血管形成.本研究构建了针对HIF-1α的pSUPER-EGFP siRNA表达载体,抑制HepG2细胞HIF-1α的表达.RT-PCR和Western blot蛋白印迹检测结果显示,RNA干扰能明显抑制HIF-1α的表达;在缺氧培养条件下,HepG2细胞中VEGF有较高的表达,当HIF-1α基因表达被有效抑制,VEGF mRNA和蛋白质的表达随之大幅下降.本研究结果表明,HIF-1α是血管生成因子VEGF表达的调节因子,通过RNA干扰导致的HIF-1α基因抑制,能下调VEGF的表达,提示HIF-1α基因可作为抗抑制VEGF依赖性的肿瘤血管生成的一个靶点.     

p53在肺癌中的表达及其与VEGF和血管新生关系的研究

目的探讨63例人肺癌中p53蛋白的表达与血管内皮细胞生长因子（VEGF）和血管新生的关系。方法采用免疫组织化学方法，以抗CD34单抗标记血管内皮细胞以测定血管新生，抗p53多抗标记p53蛋白．抗VEGF^165单克隆抗体检测VEGF的表达。结果所有肺癌组织均有不同程度的血管新生，iMVD4～138．7（44．5±29）／×400，p53突变率为54％（34／63），VEGF的表达率为50．8％（32／63）。p53突变率与组织类型、临床分期、病人性别、年龄等临床参数无关；VEGF与组织类型、临床分期、病人性别、年龄等临床参数无关。结论p53蛋白表达与VEGF和血管新生未见相关；人肺癌的发生发展与p53蛋白过度表达有关。     

HIF-1α、VEGF在胎儿生长受限患者胎盘组织中的表达及意义

目的通过探讨缺氧诱导因子1α(HIF-1α),靶基因血管内皮生长因子(VEGF)在胎儿生长受限(FGR)患者胎盘组织中的表达,研究FGR的发病机制。方法采用链酶菌抗生物素蛋白-过氧化物酶连接(SP)法检测FGR组和对照组的胎盘组织中的HIF-1α、VEGF的表达,并进行相关性分析。结果①FGR组胎盘组织中HIF-1α阳性表达率明显高于对照组,差异具有统计学意义(P<0.05)。②FGR组胎盘组织中VEGF阳性表达率低于对照组,两者比较,差异有统计学意义。③FGR组患者和对照组胎盘中HIF-1α表达与VEGF变化呈显著负相关(r=-0.622,P<0.05)。结论 HIF-1α在FGR患者胎盘组织中表达升高,通过下调靶基因VEGF,引起VEGF降低,影响胎盘血管重铸,参与胎儿生长受限的发生和发展。     

HIF-1α、VEGF及CD34在大鼠骨关节炎模型软骨中的表达及意义

目的检测低氧诱导因子(HIF-1α)、血管内皮细胞生长因子(VEGF)及CD34在膝骨关节炎(OA)软骨中的表达。方法 60只Wister大鼠,鼠龄3个月,体质量约200~250 g。随机分为实验组45只和对照组15只。实验组行单膝前交叉韧带切断术,对照组不做处理,作为空白组对照;术后9周处死动物,采用免疫组织化学苏木精-伊红(HE)染色对实验组和对照组HIF-1α、VEGF、CD34表达进行检测。结果 HIF-lα、VEGF、CD34在实验组中阳性表达率分别为66.67%(30/45)、73.33%(33/45)、71.11%(32/45),均明显高于对照组;两组数据之间的差异有统计学意义(P0.05)。实验组HIF-1α、VEGF、CD34阳性细胞计数显著高于对照组(P0.05);HIF-1α与VEGF、CD34表达存在正相关(r=0.249、0.289,P0.05)。结论 OA软骨中HIF-1α、VEGF及CD34高表达,HIF-1α与VEGF、CD34表达存在正相关,且HIF-1α、VEGF与CD34在OA软骨退行性变进展中共同发挥着重要作用。     

HIF-1α和VEGF在宫颈癌中的表达及相关性研究

目的：探讨缺氧诱导因子-1α（HIF-1α）及血管内皮生长因子（VEGF）在宫颈癌发生发展过程中蛋白表达情况及两者的相关性。方法：应用免疫组织化学S-P方法检测10例正常宫颈（NCE）、18例宫颈上皮内瘤变（CIN）、77例宫颈癌（ICC）组织中HIF-1α和VEGF蛋白的表达情况。结果：在正常宫颈上皮、宫颈上皮内瘤变组织、宫颈癌（Ⅰ—ⅡA期）组织中，HIF．1d蛋白的阳性表达率分别是0．00％、33．33％、70．13％（P〈0．05），VEGF蛋白的阳性表达率分别为10．00％、44．44％、74．00％（P〈0．05）；且随HIF—1α表达增强，VEGF阳性表达率递增，两者呈正相关（P〈0．05）。结论：HIF-1α及VEGF的表达与宫颈癌的发生发展密切相关且两者呈正相关，HIF-1α蛋白可能以转录激活的形式上调VEGF基因的表达，诱导血管生成，促进了宫颈癌的发生发展。     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

即早基因c-fos与脑血管病及学习记忆

即早基因c-fos是广泛存在于原核细胞和真核细胞的高度保守基因.在正常情况下,c-fos基因参与细胞生长、分化、信息传递、学习和记忆等生理过程,而在病理情况下c-fos基因表达及调控变化与多种疾病的发生和发展有关.C-fos在中枢神经系统的某些部位可有基础水平的表达,但表达很低,当受到如脑缺血、脑出血、痫性发作、应激等刺激后,其在数十分钟内做出反应,在对外界刺激-转录耦联的信忠传递过程中起着核内第三信使的重要作用.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.