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Preeclampsia (PE) is a serious gestational idiopathic hypertensive disease, threatening both maternal and foetal safety. As a systemic disease, the initial-onset symptoms (IOSs) and clinical manifestations of PE can vary widely from patient to patient. However, a lack of evidence-based data on IOS and their relationship to their corresponding clinical features and pregnancy outcomes persists. We hypothesised that there would be a significant difference between the morbidity time, subsequent organ dysfunction and the status of mother and foetus in PE patients with different IOS. Moreover, early identification of the characteristics of the PE patients with different IOS could improve pregnancy outcomes through individualised prevention or intervention. This study aimed to analyse maternal and foetal condition and pregnancy outcomes of PE patients with different IOS, and to explore the disease progression and characteristics of maternal and foetal outcomes for different IOS, so as to provide the basis for future maternal and foetal monitoring of PE patients.Impact statementWhat is already known on this subject? In 2013, the American College of Obstetricians and Gynecologists revised their definition of PE, sparking a heated debate. Subsequently in 2015, China updated its guidelines to define PE as hypertensive pregnancy accompanied by involvement of any other organ or organ system, to include the heart, lungs, liver and kidneys, among others. However, IOS can be varied in PE, so the maternal management and foetal monitoring should be classified through different IOS. No evidence-based data on IOS in PE patients exist.Whatthe results of this study add? Significant differences in mean morbidity times and mean delivery times were demonstrated among patients with different IOS; medians of the interval from morbidity to delivery were between 4 and 6 weeks. Significant differences in laboratory values were found in patients with different IOS. In patients that did not present with proteinuria as an IOS, 89.1% experienced proteinuria following diagnosis. Patients with the most severe complications presented with hypertension as an IOS. Follow-up visits demonstrated different foetal weight medians.Whatthe implicationsareof these findings for clinical practice and/or furtherresearch? IOS could be an indicator to help evaluate the potential for different maternal and foetal complications and PE outcomes. Moreover, the duration of treatment for PE maybe 4-6 weeks. [ABSTRACT FROM AUTHOR]

Introduction: Excessive constriction of placental chorionic plate arteries (CPAs) may be associated with preeclampsia (PE). Nitric oxide (NO) as well as intermediate and small Ca2+-activated K+ channels (IKCa and SKCa) plays vital roles in vasodilation of CPAs. We hypothesized that dysregulated IKCa and SKCa channels may be involved in the pathogenesis of PE mediated by the impaired NO system on CPAs.Methods: The location of IKCa and SKCa channels, activities of NO synthases (NOS), and expression levels of these molecules were studied on CPAs from 30 normal pregnancies and 30 PE. The vasodilating function of CPAs was measured under openers or blockers of IKCa/SKCa channels in the presence or absence of NO donor or inhibitor.Results: IKCa and SKCa channels were located both on endothelium and on smooth muscles of CPAs and the expressions of them were downregulated in PE women comparing to those in normal pregnant women. The protein expressions of endothelial NOS (eNOS) and inducible NOS (iNOS) were downregulated on CPAs in PE accompanied by decreased activity of eNOS. Notably, the vasodilatory functions mediated by IKCa/SKCa channels and by NO were aberrant on preeclamptic CPAs. In addition, IKCa and SKCa channels were responsible for nitric oxide (NO)-attributable vasorelaxation and activity modulation of NO synthases.Conclusions: This study provides evidence that dysregulated IKCa and SKCa channels might contribute to fetal pathogenesis of PE through direct promotion of vascular constriction of CPAs and through affecting functions of NO and activities of NOS. [ABSTRACT FROM AUTHOR]

Serotonergic neurons play a major role in the modulation of emotion and behaviour. Especially knockout studies have revealed a role for the serotonin1A (5-HT1A) receptor in anxiety related behaviour. Mutant animals exhibit enhanced anxiety-like responses, possibly resulting from impaired autoinhibitory control of midbrain serotonergic neurons.To further elucidate the role of the 5-HT1A receptors in affective behaviour, a complementary approach has been used and transgenic mice overexpressing this receptor subtype have been generated. The expression of the active 5-HT1A receptor protein as indicated by autoradiography was transiently increased during early postnatal development (P1.5) as compared to wild-type mice. Within the next 2 weeks, the increase in receptor binding vanished and was also not apparent in adult animals indicating adaptive changes in the regulation of 5-HT1A receptor expression. Although no evidence for increased receptor binding in the brains of adult homozygous mice was found by autoradiography, typical phenotypic changes indicative of 5-HT1A receptor overactivity were apparent. Transgenic mice revealed a reduced molar ratio of 5-hydroxyindoleacetic acid to serotonin in several brain areas and elevated serotonin values in the hippocampus and striatum. Moreover, anxiety-like behaviour was decreased in male and female transgenic mice and body temperature was lowered in male transgenic mice in comparison with heterozygous and wild-type mice. These findings further underline the pivotal role of 5-HT1A receptors in the homeostasis of anxiety-like behaviour and the crucial importance of stimulation of the 5-HT1A receptor during the early postnatal development for normal anxiety-like behaviour throughout life. [Copyright &y& Elsevier]

Introduction: Excessive constriction of placental chorionic plate arteries (CPAs) may be associated with preeclampsia (PE). Nitric oxide (NO) as well as intermediate and small Ca 2+ -activated K + channels (IK Ca and SK Ca ) plays vital roles in vasodilation of CPAs. We hypothesized that dysregulated IK Ca and SK Ca channels may be involved in the pathogenesis of PE mediated by the impaired NO system on CPAs., Methods: The location of IK Ca and SK Ca channels, activities of NO synthases (NOS), and expression levels of these molecules were studied on CPAs from 30 normal pregnancies and 30 PE. The vasodilating function of CPAs was measured under openers or blockers of IK Ca /SK Ca channels in the presence or absence of NO donor or inhibitor., Results: IK Ca and SK Ca channels were located both on endothelium and on smooth muscles of CPAs and the expressions of them were downregulated in PE women comparing to those in normal pregnant women. The protein expressions of endothelial NOS (eNOS) and inducible NOS (iNOS) were downregulated on CPAs in PE accompanied by decreased activity of eNOS. Notably, the vasodilatory functions mediated by IK Ca /SK Ca channels and by NO were aberrant on preeclamptic CPAs. In addition, IK Ca and SK Ca channels were responsible for nitric oxide (NO)-attributable vasorelaxation and activity modulation of NO synthases., Conclusions: This study provides evidence that dysregulated IK Ca and SK Ca channels might contribute to fetal pathogenesis of PE through direct promotion of vascular constriction of CPAs and through affecting functions of NO and activities of NOS., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: The human papillomavirus type 16 (HPV16) early gene (E5) could stimulate cell proliferation and transformation in different ways, and complement or enhancement the function of E6 and E7. It is closely sodiated with the carcinogens of cervical cancer. This study was to investigate the effects of HPV16 E5 on the human cervical cancer cell line SiHa., Methods: The sense sequence of HPV16 E5 was cloned into eukaryotic expression vector pEGFP-C1 to prepare recombinant plasmid, which was stable transfected into SiHa cells. The mRNA and protein levels of E5 and p21 gene were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Cell proliferation after stable transfection was evaluated by MTT assay. The tumorigenesis of SiHa/16E5 cells was assessed both in vitro and in vivo by soft agar clone form test and naked mouse form test., Results: After stable transfection of HPV16 E5 sense DNA, the mRNA and protein levels of HPV16 E5 in SiHa cells were obviously increased, but that of P21 were decreased. The proliferation activity of SiHa/16E5 cells was significantly higher than that of SiHa/pEGFP-C1 and SiHa cells (P < 0.05). The clone numbers of SiHa/16E5 cells, were significantly more than SiHa/pEGFP-C1 and SiHa cells [(33.4 +/- 1.6) vs (15.1 +/- 3.1), (16.3 +/- 2.5), P < 0.05] in vitro. The growth of tumors on naked mouse was much faster in SiHa /16E5 group than those in the SiHa/pEGFP-C1 and SiHa cells groups (P < 0.05)., Conclusion: HPV16 E5 decreased the expression of P21 in SiHa cells, and enhancement the proliferation of SiHa cells and the ability of tumorigenesis.

Background & Objective: Peptidyl-prolyl cis/trans isomerase Pin1 is prevalently overexpressed in human cancers. Up-regulation of Pin1 elevates the expression of Cyclin D1, and plays an important role in tumorigenesis and tumor progression. This study was to investigate the expression and clinical significance of Pin1 and Cyclin D1 in cervical cancer cell lines and cervical epithelial tissues., Methods: The expression of Pin1 and Cyclin D1 in cervical cancer cell lines HeLa, SiHa, C33a and Caski were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Their expression in 88 samples of cervical tissues, including 10 samples of normal cervix, 21 samples of cervical intraepithelial neoplasia (CIN), and 57 samples of invasive cervical cancer, were detected by immunohistochemistry., Results: The mRNA and protein levels of Pin1 were significantly higher in HeLa, SiHa, C33a, and Caski cells than in normal cervical epithelial tissues (P<0.05). The expression of Pin1 increased progressively along with the disease process from normal cervix to CIN, and to invasive cervical cancer (0%, 47.62%, 64.91%, P<0.05). Pin1 expression had no relation to disease stage (FIGO), pathologic grade, and pelvic lymph node metastasis status (P>0.05). The positive rate of Pin1 was significantly higher in cervical adenocarcinoma than in cervical squamous cell carcinoma (100% vs. 60.0%, P<0.05). In cervical cancer tissues, the overexpression of Pin1 was positively correlated to that of Cyclin D1 (P<0.05)., Conclusions: Pin1 is overexpressed in HeLa, SiHa, C33a and Caski cell lines as well as in cervical cancer tissues. The overexpression of Pin1 is closely related to Cyclin D1 expression in cervical cancer. The aberrant expression of Pin1 and Cyclin D1 might contribute to tumorigenesis of cervical cancer.

The effects of brain-derived neurotrophic factor (BDNF) on the development of presynaptic terminals and of neuronal subtypes in various brain areas were studied in BDNF-knockout (BDNF-/-) mice at postnatal days 15-17. Western analysis revealed no changes in the overall amount of a variety of synaptic proteins in BDNF-/- mice as compared to wild type mice. In addition, the complex between the vesicular proteins, synaptophysin and synaptobrevin, as well as their respective homodimers were unaltered. Moreover, no changes in the density of neurons were found in, e.g., the CA3 region of the hippocampus and the nucleus nervi facialis of BDNF-/- mice. However, cholinergic cells were reduced by 20% in the medial septum of BDNF-/- mice associated with a decrease in the activity of choline acetyltransferase and protein levels of nerve growth factor in the hippocampus by 16% and 44%, respectively. In the striatum, however, the total number of cholinergic cells were comparable in both groups, although the activity of choline acetyltransferase was decreased by 46%. In GABAergic interneurons, the expression of neuropeptides in various brain areas was differentially affected by BDNF deletion as revealed by immunohistochemistry. In the hippocampus and cortex of BDNF-/- mice, the density of neuropeptide Y-, somatostatin-, and parvalbumin-immunoreactive cells was drastically reduced, whereas the density of calretinin-positive cells was increased. The extent of these changes in neuropeptide-containing cells varied among hippocampal subregions. In the striatum, only the density of parvalbumin-immunoreactive cells was decreased by approximately 45%. In conclusion, BDNF deficiency is accompanied by a differential dysregulation in the expression of neuropeptides and calcium-binding proteins in otherwise intact GABAergic and glutamatergic neurons in a region-specific manner.