Efectividad en la suplementación con omega 3 (Pescado) y vitamina D durante el periodo gestacional para la prevención de diversas alergias en el lactante de 0-1 año de edad / Effectiveness in the omega 3 (Fish) and vitamin D supplementation during the gestational period for the prevention of various allergies in the 0-1 year old infant / Eficácia na suplementação de ômega 3 (peixe) e vitamina D durante o período gestacional para a prevenção de várias alergias na criança de 0 a 1 ano

Resumen El objetivo de esta investigación fue describir la efectividad de la suplementación con omega 3 (pescado) y vitamina D durante la etapa gestacional para la prevención de diversas alergias en el lactante de 0 a 1 año. Se presenta los resultados de una compilación y categorización de la mejor evidencia científica disponible. Se aplicó la metodología sugerida para la práctica clínica basada en la evidencia, la cual inició con el establecimiento de una pregunta clínica seguido por la búsqueda de la información en las bases de datos Medline, Science Direct y Cochrane Library, obteniendo 334 artículos de los cuales al aplicar los criterios de selección se conservan 9. Luego se llevó a cabo un análisis crítico utilizando la plataforma FLC 2.0 y clasificando la evidencia por su calidad y grados de recomendación según Canadian TaskForce on Preventive Health Care.Se concluye que a pesar de que los beneficios de la vitamina D y el omega 3 son múltiples, y que el uso en conjunto de ambos en el embarazo, podría significar una mejora no solo sobre la salud materna sino también sobre el feto y lactante; al no contar con estudios con resultados contundentes, no se puede generalizar o recomendar en la práctica clínica.

Abstract The objective of this research was to describe the effectiveness of omega 3 (fish) and vitamin D supplementation during the gestational stage for the prevention of various allergies in infants aged 0 to 1 year. The results of a compilation and categorization of the best available scientific evidence are presented. The methodology suggested for the clinical practice based on the evidence was applied, which began with the establishment of a clinical question followed by the search of the information in the Medline, Science Direct and Cochrane Library databases, obtaining 334 articles of which when the selection criteria are applied, they are kept 9. Then, a critical analysis was carried out using the FLC 2.0 platform and the evidence was classified by its quality and degrees of recommendation according to the Canadian Task Force on Preventive Health Care. It is concluded that although the benefits of vitamin D and omega 3 are multiple, and that the joint use of both in pregnancy, could mean an improvement not only on maternal health but also on the fetus and infant; By not having studies with conclusive results, it can not be generalized or recommended in clinical practice.

Resumo O objetivo desta pesquisa foi descrever a eficácia da suplementação de ômega 3 (peixe) e vitamina D durante o estágio gestacional para a prevenção de várias alergias em lactentes de 0 a 1 ano de idade. Os resultados de uma compilação e categorização das melhores evidências científicas disponíveis são apresentados. Foi aplicada a metodologia sugerida para a prática clínica baseada na evidência, que começou com o estabelecimento de uma questão clínica seguida pela busca da informação nos bancos de dados da Medline, Science Direct e Cochrane Library, obtendo 334 artigos dos quais quando os critérios de seleção são aplicados, eles são mantidos 9. Então, uma análise crítica foi realizada usando a plataforma FLC 2.0 e a evidência foi classificada por sua qualidade e graus de recomendação de acordo com a Canadian Task Force on Preventive Health Care. Conclui-se que, embora os benefícios da vitamina D e omega 3 sejam múltiplos e que o uso conjunto de ambos na gravidez, pode significar uma melhora não só na saúde materna, mas também no feto e no bebê; Ao não ter estudos com resultados conclusivos, não pode ser generalizada ou recomendada na prática clínica.

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease / Avaliação do Polimorfismo da Galectina-3 em Indivíduos com Doença de Chagas Crônica

AbstractBackground:Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated.Objective:The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.Methods:Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.Results:For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease.Conclusion:Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0).

ResumoFundamento:A galectina-3, uma lectina de ligação à β-galactosidase, foi descrita como um mediador de fibrose cardíaca em estudos experimentais e um fator de risco associado com eventos cardiovasculares em indivíduos com insuficiência cardíaca. Estudos prévios avaliaram a susceptibilidade genética para doença de Chagas em humanos, incluindo polimorfismos dos genes de citocinas, demonstrando correlações entre o polimorfismo genético e o desenvolvimento de cardiomiopatia na fase crônica. No entanto, a relação entre polimorfismos de nucleotídeo único (single nucleotide polymorphism, SNP) e variações fenotípicas na doença de Chagas ainda não foi avaliada.Objetivo:O presente estudo teve como objetivo determinar se os polimorfismos genéticos da galectina-3 podem predispor ao desenvolvimento de formas cardíacas da doença de Chagas.Métodos:Cinquenta e cinco indivíduos com doença de Chagas foram incluídos neste estudo observacional. A genotipagem das variantes rs4644 e rs4652 do gene da galectina-3 foi realizada por PCR (reação em cadeia de polimerase).Resultados:Para o SNP rs4644, não houve associação entre o risco relativo para a forma cardíaca e os genótipos AA (OR = 0,79, p = 0,759), AC (OR = 4,38, p = 0,058), ou CC (OR = 0,39, p = 0,127). Similarmente, para o SNP rs4652, não foi encontrada associação entre os genótipos AA (OR = 0,64, p = 0,571), AC (OR = 2,85, p = 0,105), ou CC (OR = 0,49, p = 0,227) e a forma cardíaca da doença.Conclusão:Nossos resultados não mostraram associação entre os diferentes genótipos para ambos SNPs do gene da galectina-3 e a forma cardíaca da doença de Chagas. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0).

Circulating miR-214 level and its correlation with the extent of coronary lesion in patients with acute myocardial infarction / 中南大学学报(医学版)

OBJECTIVE@#To examine the circulating levels of miR-214 in acute myocardial infarction (AMI) patients and to explore the relationship between the circulating levels of miR-214 and the degree of coronary lesion.@*METHODS@#A total of 45 patients with AMI (AMI group) were enrolled from Xiangya Hospital of Central South University between September, 2011 and January, 2012. Twenty healthy volunteers served as a normal control group (n=20). According to the coronary artery lesion area, AMI group was also divided into a single-branch group, a double-branch group and a triple-branch group (n=20, 13, 12 respectively). Circulating levels of miR-214 and plasma levels of placental growth factor (PLGF) were measured by real time-PCR assay and enzyme-linked immunosorbent assay respectively on the day when the patients admitted to the hospital. The plasma levels of miR-214 and PLGF were compared among the various branch groups. The correlation between miR-214 and PLGF was analyzed in AMI subgroups.@*RESULTS@#The miR-214 levels in the AMI subgroups were lower than that in the control group. The more decrease in miR-214 level, the larger size of coronary lesion. There was significant difference in the different groups (all P<0.05). Compared with the control group, the levels of plasma PLGF were significantly higher in the AMI subgroups. The more increase in PLGF level, the larger size of coronary lesion. There was significant difference in the different groups (all P<0.05). The plasma levels of miR- 214 were negatively correlated with that of PLGF in the AMI group (r=-0.588, P<0.01).@*CONCLUSION@#The circulating level of miR-214 was significantly decreased in the AMI group, which might be correlated with the extent of the coronary lesion. Circulating miR-214 may be a promising biomarker for the diagnosis and prognosis of severe AMI.

Expression of progesterone-induced blocking factor in severe preeclampsia and its association with immune tolerance imbalance / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore progesterone-induced blocking factor (PIBF) expression in the placenta and blood of patients with severe preeclampsia and its relationship with immune tolerance imbalance.</p><p><b>METHODS</b>Forty-seven patients admitted between January and December, 2012 were enrolled in this study, including 25 patients with early-onset severe preeclampsia (EOPE) and 22 with late-onset severe preeclampsia (LOPE), with 25 women with normal pregnancy serving as control group. The antenatal blood and postpartum placenta were collected for immunohistochemical staining to detect PIBF expression in the placenta and for testing serum PIBF level using ELISA. Flow cytometry was used to detect the percentage of circulating Th1 and Th2 cells and the Th1/Th2 ratio was calculated.</p><p><b>RESULTS</b>PIBF was expressed in decidual cells, syncytiotrophoblasts and partial cytotrophablasts. The serum PIBF levels were 213.58 ± 44.93 ng/ml in EOPE group, 243.00∓61.19 ng/ml in LOPE group and 273.91 ± 48.57 ng/ml in control group. There were significant differences in serum PIBF, blood Th1/Th2 and placenta PIBF-IOD among the 3 groups (P<0.05). EOPE group had significantly lower serum PIBF, lower llacental PIBF quantity (PIBF-IOD) and higher blood Th1/Th2 than the control group (P<0.05). Serum PIBF in women with severe preeclampsia was positively correlated with placenta PIBF-IOD and negatively with blood Th1/Th2 ratio (P<0.05), but a negative correlation between serum PIBF and 24-hour urinary protein was found only in EOPE group (P<0.05).</p><p><b>CONCLUSION</b>The immune tolerance imbalance mediated by PIBF may participate in the pathogenesis of severe preeclampsia. PIBF, the immune suppressor secreted by lymphocytes of pregnancy women, is also a protective factor against severe preeclampsia, which is expected to be a new target in therapy.</p>

Identification of pregnancy-associated glycoproteins by peptide mass fingerprinting in water buffalo (Bubalus bubalis).

Ruminant placentas synthesize pregnancy-associated glycoproteins (PAGs) during pregnancy, which serve as biomarkers of pregnancy. The present study was conducted to verify, whether PAGs are expressed in buffalo placenta by using lectin-based affinity chromatography and peptide mass finger printing (PMF). Fetal cotyledonary tissues were collected from gravid uteri procured from slaughtered house. Proteins were extracted and subjected to wheat germ agglutinin (WGA) lectin affinity chromatography to isolate the PAGs. The isolated glycoproteins were separated by one-dimensional SDS-PAGE. PMF results of the 75 kDa protein revealed presence of two PAGs (PAG-7 and -11). The PAG-7 consisted of about 170 mass signals, of which 16 were assigned to corresponding/translated cDNA sequences of buffalo PAG-7, leading to sequence coverage of 40%. PMF result of PAG-11 showed 170 mass signals, of which 15 were assigned to buffalo PAG-11, leading to sequence coverage of 34%. In conclusion, the glycoprotein isolated from placental extract corresponding to 75 kDa band on SDS PAGE gel was a mixture of PAG-7 and -11, which may help in development of suitable diagnostics for pregnancy in buffalo.

Effects of placental growth factor on revascularization after acute myocardial infarction in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of placental growth factor (PlGF) on revascularization after acute myocardial infarction.</p><p><b>METHODS</b>Myocardial infarction model was established by ligation of left anterior descending coronary artery in Wistar rats. Thirty AMI rats were divided into 3 groups with 10 in each group: PlGF, mouse VEGFR-1/Flt-1 antibody, or saline (control group) was injected in the infarcted border zone for each group, respectively. Two weeks later the hemodynamics parameters were measured with a left ventricular needle catheter and a biological signal analysis system; left ventricular remodeling was observed by HE staining; angiogenesis was examined by immunohistochemistry and cardiomyocyte apoptosis rate was detected by TUNEL.</p><p><b>RESULTS</b>The stroke volume, systolic pressure and left ventricular developed pressure in PlGF group were all higher than those in control group (112±7 vs 65.63±8.50 μl, P<0.01; 131.61±9.26 vs 94.84±8.53 mm Hg, P<0.01 and 175.85±11.36 vs 105.50±15.83 mm Hg, P<0.01; respectively). PlGF animals had less ventricular dilation (left ventricular diameter 8.20±0.14 vs 9.25±0.32 mm, P<0.01) and increased left ventricular wall thickness (1.81±0.10 vs 1.35±0.10 mm, P<0.01) compared to controls. The geometry parameter of anti-VEGFR1 and control animals was almost the same. PlGF animals had increased angiogenesis compared to controls (29.44±5.75 vs 15.88±2.42 endothelial cells/high-powered field, P<0.01); the alpha smooth muscle actin (α-SMA) showed that PlGF animal had a higher density of artery than others (25.14±1.83 vs 19.70±2.52 arteries/mm(2), P<0.01), and the density of artery in anti-VEFGR1 group was less than the controls. The apoptosis rate of cardiomyocytes in PlGF animals was significantly lower than that in controls (9.51%±2.75% vs 37.81%±8.74%, P<0.01).</p><p><b>CONCLUSION</b>Regional delivery of PlGF following acute myocardial infarction can improve cardiac function and left ventricular remodeling, enhance angiogenesis and reduce cardiomyocyte apoptosis rate. PlGF may be a potential agent in adjuvant therapy for acute myocardial infarction.</p>

Relationship between fetal growth restriction and angiogenesis factors / 南方医科大学学报

Placenta is an important organ to maintain fetal growth, metabolism, maternal and fetal physiologic balance. Angiogenesis is a critical factor in placental development involved in fetal blood circulation and vascular changes in the endometrium and placenta. Angiogenesis is closely related to angiogenesis factors such as vascular endothelial growth factor and placenta growth factor. Fetal growth restriction threats the fetal health in gestation and also increases the long-term likeliness of several diseases. In this review, the authors summarize the findings in current studies of the relationship between angiogenesis factors and fetal growth restriction.

Expression of soluble vascular endothelial growth factor receptor-1 and placental growth factor in fetal growth restriction cases and intervention effect of tetramethylpyrazine

OBJECTIVE@#To investigate the expression of soluble vascular endothelial growth factor receptor-1 (sFlt-1) and placental growth factor (PLGF) in the fetal growth restriction (FGR) cases and the intervention mechanism of tetramethylpyrazine.@*METHODS@#A total of 60 fetal growth restriction cases that admitted to our hospital were randomly divided into ligustrazine intervention group (group A) and nutritional support group (group B). A total of 50 healthy pregnant women were also enrolled as control group (group C). Expression level of maternal serum sFlt1, PLGF and fetal growth parameters including HC, AC, FL, BPD, EFW as well as placenta PLGF, sFlt-1 mRNA expression were recorded and compared among the three groups. A total of 15 SD rats were selected and were divided into three groups, TMP group, alcohol and tobacco group and blank control group. Three groups of rats were dissected on the twentieth day of gestation.@*RESULTS@#Expression level of sFlt-1 and PLGF in group A was not significantly different from that of group C (P>0.05); but significant difference in SFlt1 and PLGF expression level was observed between group C and group B (P0.05). There was significant difference in PLGF between FGR group with treatment and FGR group without treatment or control group (P<0.01).@*CONCLUSIONS@#PLGF level is decreased and sFlt-1 increased in patients suffered from fetal growth restriction, and FGR rats show increased sFlt-1 and decreased PLGF, thus they can be indicator of the fetal growth restriction. Ligustrazine can effectively improve sFlt-1, PLGF expression level in fetal growth restriction cases, which can be used as treatment for FGR.

Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant woman with recurrent spontaneous abortion / 华中科技大学学报（医学）（英德文版）

The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.

Role of nitric oxide, angiogenic growth factors and biochemical analysis in preeclampsia.

Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal mortality and morbidity globally. Angiogenic growth factors, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are involved in the generation of new blood vessels required for placental development and physiological functions, while nitric oxide (NO) acts as vasodilator and also plays a role in angiogenesis. The objective of this study was to evaluate the role of NO, angiogenic growth factors (VEGF and PIGF) and other biochemical parameters in the development of preeclampsia among pregnant mothers. A complete clinical history, including anthropometric measurements and biochemical investigations, including renal function tests, liver function tests and lipid profile were performed among twenty preeclampsia patients aged 19 to 32 yrs. Results were compared with age-matched normotensive pregnant mothers. The body weight, body mass index (BMI), blood pressure, concentrations of urea, uric acid and triglyceride and activities of transaminase enzymes (aspartate transaminase, AST and alanine transaminase, ALT) in serum were significantly higher (p<0.05) than normotensive subjects. Serum concentrations of VEGF, PlGF and NO were significantly decreased (p<0.005) in preeclamptic patients. NO was found negatively correlated with body weight (r = -0.369, p<0.05), systolic blood pressure (r = -0.822, p<0.005), diastolic blood pressure (r = -0.714, p<0.005) and was positively correlated with VEGF (r = 0.464, p<0.005) and PlGF (r = 0.546, p<0.005). VEGF and PlGF showed significant (p<0.005) negative correlation with systolic and diastolic blood pressure and PlGF was significantly correlated with triglyceride (r = -0.379). However, no significant correlation was observed between the VEGF and PlGF. In conclusion, the results indicated that body weight, triglyceride, angiogenic growth factors and NO might associate with preeclampsia development.

The VEGF signaling pathway in cancer: the road ahead / 癌症

The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.

Blockade of VEGFR-1 and VEGFR-2 Enhances Paclitaxel Sensitivity in Gastric Cancer Cells

PURPOSE: Hypoxia-inducible factor-1alpha (HIF-1alpha) increases transcription of the vascular endothelial growth factor (VEGF) gene. Inhibition of VEGF abolishes VEGF mediated induction of HIF-1alpha. Recent reports suggested that HIF-1alpha also mediated the induction of class III beta-tubulin (TUBB3) in hypoxia. TUBB3 confers resistance to taxanes. Inhibition of VEGF may decrease the expression of HIF-1alpha and TUBB3. This study was undertaken to investigate the roles of vascular endothelial growth factor receptor (VEGFR) in gastric cancer cell behavior and to identify methods to overcome paclitaxel resistance in vitro. MATERIALS AND METHODS: The protein expression levels of HIF-1alpha and TUBB3 were measured in human gastric cancer cell lines (AGS) under normoxic and hypoxic conditions. The relationship between TUBB3 and paclitaxel resistance was assessed with small interfering TUBB3 RNA. AGS cells were treated with anti-VEGFR-1, anti-VEGFR-2, placental growth factor (PlGF), bevacizuamb, and paclitaxel. RESULTS: Hypoxia induced paclitaxel resistance was decreased by knockdown of TUBB3. Induction of HIF-1alpha and TUBB3 in AGS is VEGFR-1 mediated and PlGF dependent. Hypoxia-dependent upregulation of HIF-1alpha and TUBB3 was reduced in response to paclitaxel treatment. Expressions of HIF-1alpha and TUBB3 were most decreased when AGS cells were treated with a combination of paclitaxel and anti-VEGFR-1. AGS cell cytotoxicity was most increased in response to paclitaxel, anti-VEGFR-1, and anti-VEGFR-2. CONCLUSION: We suggest that blockade of VEGFR-1 and VEGFR-2 enhances paclitaxel sensitivity in TUBB3-expressing gastric cancer cells.

Prediction of pre-eclampsia during early pregnancy in primiparas with soluble fms-like tyrosine kinase-1 and placental growth factor.

Background. We hypothesized that pre-eclampsia (PE) can be predicted early in primiparas by measuring serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Methods. All normotensive primiparas attending the antenatal clinics of Aga Khan University Hospital and Aga Khan Hospital for Women, Karachi, Pakistan without any known risk factor for PE were invited to participate in the study. They were divided into two groups based on the development of PE. Their blood samples were collected at 8–15, 16–22, 23–28, 29– 34 weeks of pregnancy and once within 1 week of delivery. All samples were analysed for sFlt-1 and PlGF. Results. Six hundred and eleven (46.7%) of 1307 recruited primiparas completed the study according to the protocol. Of these, 39 (6.4%) women developed PE. The difference in serum sFlt-1 was evident as early as 15 weeks of gestation. Higher levels of serum sFlt-1 were present in women who later developed PE. Relatively higher levels of PlGF were observed in non-PE women compared to PE women up to 22 weeks of gestation. However, after 23 weeks of pregnancy, PlGF levels increased in both the groups, but less so in the PE group. Receiver operator characteristics (ROC) curve analysis showed that even in early pregnancy (<15 weeks of gestation), serum sFlt-1 alone has the potential to predict PE with area under the curve (AUC), sensitivity and specificity of 0.81, 75.9 and 72.4, respectively. Conclusion. PE can be predicted in primiparas in the early part of second trimester with serum levels of sFlt-1 and in the later part of second trimester with serum levels of PlGF.

Expression of Placenta Growth Factor in Colorectal Carcinomas

PURPOSE: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. PlGF is implicated in several pathologic processes, including the growth and spread of cancer and tumor angiogenesis. The aim of this study was to evaluate the expression and the clinical implications of PlGF in colorectal cancer. METHODS: In order to ascertain the clinical significance of PlGF expression in colorectal cancer, the researcher analyzed the expression pattern of PlGF by using an immunohistochemical method and attempted to establish if a relationship existed between PlGF expression and microvessel density (MVD), and subsequently between PlGF expression and the predicted prognosis. A total of 83 patients with colorectal cancer were included for immunohistochemical staining. Clinicopathological characteristics were defined according to the tumor-node-metastasis (TNM) criteria of the Union for International Cancer Control. Clinicopathologic factors, such as age, sex, histological types of tumors, tumor cell grade, TNM stage, lymphovascular invasion, and lymph-node metastasis, were reviewed. RESULTS: In this study, the PlGF protein expression level was significantly correlated with MVD, patient survival, and clinicopathological factors such as lymph-node metastasis, TNM staging, lymphatic invasion and vascular invasion. CONCLUSION: PlGF may be an important angiogenic factor in human colorectal cancer, and in this study, PlGF expression level was significantly correlated with positive lymph-node metastases, tumor stage, and patient survival. These findings suggest that PlGF expression correlates with disease progression and may be used as a prognostic marker for colorectal cancer.

Role of placenta growth factor in cancer and inflammation

Accumulating evidences have documented that angiogenesis is closely linked to inflammation and regulators of angiogenesis play key roles in various inflammatory conditions. PlGF is an angiogenic protein belonging to the VEGF family and is upregulated mainly in pathologic conditions. Recently, PlGF was discovered having a proinflammatory role in inflammatory arthritis and its serum level drew attention not only as a useful surrogate biomarker but also a potential therapeutic target in atherosclerosis and various cancers. Particularly, PlGF has attractive clinical values because endogenous PlGF is redundant for vascular development and physiological vessel maintenance in healthy adults. However, there have been conflicting results about the efficacy of PlGF inhibition depending on the experimental and clinical settings. Further close investigations for resolving the puzzle of PlGF biology are required.

The discovery of placenta growth factor and its biological activity

Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration. Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placenta growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1, also known as Flt-1) and VEGF receptor 2 (VEGFR-2, also known as Flk-1 in mice and KDR in human) have a decisive role. In this review, we describe the discovery and molecular characteristics of PlGF, and discuss the biological role of this growth factor in physiological and pathological conditions.

Niveles de proteína c-reactiva en gestantes con y sin periodontitis crónica del Instituto Nacional Materno Perinatal / C-reactive protein levels in pregnant women with and without chronic periodontitis in Maternal Perinatal National Institute

Objetivo. Evaluar los niveles de Proteína C-Reactiva (PC-R) en gestantes con y sin periodontitis crónica teniendo en cuenta la covariable infección genito urinaria. La PC-R ha estado implicada como posible mediador inflamatorio sistémico en la asociación de periodontitis y efectos adversos en el embarazo. Material y método. Fueron medidos los niveles de PC-R con la técnica de inmuno turbidimetría a un total de 48 gestantes, 33 con periodontitis crónica y 15 sin periodontitis crónica según los criterios de la Asociación Americana de Periodoncia. Resultados. Se encontraron diferencias significativas (p=0,04), en los niveles de PC-R entre las gestantes con periodontitis (5,13 ± 4,47 mg/L) y sin periodontitis crónica (3,05 ± 2,41mg/L) siendo mayores los niveles de PC-R en las gestantes con periodontitis crónica. Conclusión. La periodontitis crónica juega un rol importante en la elevación de los niveles de proteína C-reactiva, lo que podría mediar la relación entre periodontitis y efectos adversos en el embarazo.

Objective. To asses plasma CRP levels in pregnant women with and without chronic periodontitis taking into account the covariate genito urinary infection C-reactive protein (CRP) has been implicated as a possible systemic inflammatory mediator of the association of periodontitis and adverse pregnancy outcomes. Material and method. The levels of PC-R were measured with immuno turbidimetric technique to a total of 48 pregnant women, 33 with chronic periodontitis and 15 without chronic periodontitis according to the criteria of the American Academy of Periodontology. Results. Significative differences were found (p=0,04), in the CRP level in pregnant women with periodontitis (5.13±4.47 mg/L and without chronic periodontitis (3.05±2.41 mg/L. We found statistical significant differences between the groups. Conclusion. Chronic periodontitis plays an important role in increasing levels of C-reactive protein and this may mediate the relationship between periodontitis and adverse pregnancy outcomes.

Circulating angiogenic factors in pregnancies complicated by pre-eclampsia.

Background. Pre-eclampsia is an inflammatory disorder characterized by diffuse endothelial dysfunction possibly secondary to impaired trophoblast invasion of the spiral arteries during implantation. It is associated with alterations in maternal serum concentrations of vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). We did a case–control study to ascertain whether pre-eclampsia is associated with changes in serum concentrations of VEGF, PlGF and sFlt-1 in Indian patients. Methods. Serum samples were obtained from 40 women with pre-eclampsia and 40 normotensive, non-proteinuric pregnant women. The levels of VEGF, PlGF and sFlt-1 were analysed using ELISA. Results. In the sera of pregnant women with pre-eclampsia, the levels of sFlt-1 were significantly higher than those in the sera of normotensive, non-proteinuric pregnant women (median 11 295.25 v. 2936.2 pg/ml, p<0.0001), whereas there was a significant reduction in the levels of free VEGF (mean [SD] 170.53 [36.56] pg/ml v. 254.61 [47.39] pg/ml, p<0.0001) and PlGF (mean [SD] 236.77 [93.70] pg/ml v. 744.98 [168.55] pg/ml, p<0.0001). Conclusion. An increase in sFlt-1 levels and a simultaneous decrease in free VEGF and PlGF levels in the sera of women with pre-eclampsia as compared with normotensive, nonproteinuric pregnant women suggest that an imbalance between the levels of these pro- and anti-angiogenic factors may have a role to play in the pathogenesis of pre-eclampsia.

Expression of PLAC1/CP1 genes in primary colorectal carcinoma and its clinical significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression and significance of PLAC1/CP1 genes in patients with primary colorectal carcinoma.</p><p><b>METHODS</b>The expression of PLAC1/CP1 genes in 97 cases of colorectal carcinoma was studied using tissue chip technology and immunohistochemistry.</p><p><b>RESULTS</b>The rate of PLAC1/CP1 proteins expression in the cases studied was 56.7% (55/97), with 27.8% (27/97) being nuclear staining and 43.3% (42/97) being cytoplasmic staining. The percentage of expression was higher in women than in men (χ(2) = 6.567, P = 0.010). The expression in poorly differentiated colorectal carcinoma was significantly higher than that in the well or moderately differentiated carcinoma (χ(2) = 8.321, P = 0.016). The expression was also significantly higher in stage TNM III or IV tumors than in stage TNM I or II tumors (χ(2) = 18.726, P = 0.000). The rate was higher in cases with lymph node metastasis than in those with negative lymph nodes (χ(2) = 17.407, P = 0.000), and was higher as the number of metastasis increasing (χ(2) = 22.632, P = 0.000).</p><p><b>CONCLUSION</b>The expression of PLAC1/CP1 genes correlates with various clinical and pathologic parameters. It carries prognostic significance and may represent a potential target for immunotherapy.</p>

Relationship between serum vasoactive factors and plaque morphology in patients with non-ST-segment elevated acute coronary syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Vasoactive factors have been reported to correlate with vulnerable plaque and acute coronary syndrome (ACS). This study aimed to investigate the relationship between vasoactive factors and plaque morphology in patients suffering from non-ST-segment elevated ACS.</p><p><b>METHODS</b>From April 2007 to April 2009, 124 consecutive patients suffering from non-ST-segment elevated ACS who had received coronary angiography (CAG) and intravascular ultrasound (IVUS) in the People's Liberation Army General Hospital and Beijing Anzhen Hospital were enrolled in this study. Three serum vasoactive factors, plasma soluble vascular endothelial growth factor receptor-1 (sFlt-1), placental growth factor (PLGF) and interleukin-18 (IL-18), were measured by enzyme-linked-immunosorbent serologic assay of the patients. The levels of vasoactive factors were compared between vulnerable plaque group and stable plaque group, and between unstable angina pectoris (UAP) group and non-ST-segment elevation acute myocardial infarction (NSTE-AMI) group. The relationship between the plaque morphology and levels of vasoactive factors was analyzed.</p><p><b>RESULTS</b>The levels of vasoactive factors were similar between the UAP group (69 patients) and NSTE-AMI group (55 patients). The levels of sFlt-1 and PLGF in the vulnerable plaque group were significantly higher than those in the stable plaque group. The level of IL-18 was correlated positively with plaque morphology. Multivariate Logistic regression analysis showed that the level of PLGF was an independent risk factor for vulnerable plaque (OR=2.115, 95% CI 1.415-5.758, P=0.018). Using the ROC curve, PLGF was a significant factor for the diagnosis of vulnerable plaque (the diagnostic point was 26.3 ng/L, the proportion of square area under the ROC curve was 0.799, 95%CI 0.758-0.839, P<0.001; the sensitivity of PLGF under the ROC curve was 86%, and the specificity 63%).</p><p><b>CONCLUSION</b>Both IL-18 and PLGF are biomarkers for vulnerable plaques and helpful to predict vulnerable plaque.</p>