scholarly journals The Small-Conductance Ca2+-Activated Potassium Channel, Subtype SK3, in the Human Myometrium Is Downregulated in Early Stages of Pregnancy

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
M. Rahbek ◽  
S. T. Rosenbaum ◽  
M. J. Dahl ◽  
D. A. Klaerke ◽  
L. Ødum ◽  
...  
Keyword(s):  
Immunohistochemical Staining ◽  
Late Pregnancy ◽  
Human Myometrium ◽  
Mrna Levels ◽  
Sk Channels ◽  
Uterine Smooth Muscle ◽  
Qrt Pcr ◽  
Endometrial Epithelium ◽  
Small Conductance ◽  
In Pregnancy

The human myometrium is mainly relaxed during pregnancy, but, up to term, contractions become more coordinated and forceful in order to initiate delivery. Small conductance Ca2+-activated K+ channels (SK channels) in human myometrium have been shown to be downregulated in late pregnancy. The aim was to investigate the presence of SK2 and SK3 in the human myometrium from nonpregnant women, pregnant women at term, and pregnancies delivered preterm and, in addition, to characterize the time of downregulation of these channels. Using qRT-PCR, we observed significantly lower levels of mRNA for SK2 than for SK3 in the nonpregnant tissue. The mRNA levels of SK3 were significantly reduced in tissue from pregnancies at term and pregnancies resulting in preterm deliveries, whereas no downregulation for SK2 was observed. Western blotting confirmed the qRT-PCR results. Using immunohistochemical staining, both SK2 and SK3 were detected in endometrial glandular epithelium. We conclude that SK3 mRNA is downregulated early in pregnancy—at least among those that result in preterm deliveries. Furthermore, we find that SK channels are expressed not only in the uterine smooth muscle but also in the endometrial epithelium.

scholarly journals Levels of corticotrophin-releasing hormone receptor subtype 1 mRNA in pregnancy and during labour in human myometrium measured by quantitative competitive PCR

1998 ◽  
Vol 21 (2) ◽  
pp. 201-208 ◽  
Author(s):  
B Rodriguez-Linares ◽  
S Phaneuf ◽  
A Lopez Bernal ◽  
EA Linton
Keyword(s):  
Housekeeping Gene ◽  
Human Myometrium ◽  
Receptor Subtype ◽  
Mrna Levels ◽  
Competitive Pcr ◽  
Direct Role ◽  
Releasing Hormone ◽  
Tissue Changes ◽  
Pcr Method ◽  
In Pregnancy

It is suggested that corticotrophin-releasing hormone (CRH) is involved in parturition. We have previously reported the presence of the CRH receptor subtype 1 (CRH R1) in human uterine myocytes. The aim of the present study was to investigate whether expression of the CRH R1 in myometrial tissue changes in pregnancy and labour. We used a quantitative competitive PCR method to measure the mRNA levels of this receptor in non-pregnant and in term pregnant myometrium before and at different stages of labour. The levels of mRNA for the housekeeping gene for glucocerebrosidase (GCB) were also determined. The results were expressed as a ratio of CRH R1 and GCB mRNA levels. We have found that in pregnancy the CRH R1 is down-regulated from a ratio of 0.093+/-0.011 in non-pregnant myometrium to 0.012+/-0.005 (P<0.001) in term non-labouring myometrium. No significant changes were observed in the CRH R1:GCB ratio in tissues sampled within 13 h (0.013+/-0.004) from the start of labour. In summary, normalised levels of CRH R1 are down-regulated in pregnancy and do not change during labour. We speculate that our results do not support a direct role for the CRH R1 receptor in myometrial stimulation.

scholarly journals Life-long persistence of infectious Zika virus: inflammation and behavioral sequela

2020 ◽  
Author(s):  
Derek D.C. Ireland ◽  
Mohanraj Manangeeswaran ◽  
Aaron Lewkowicz ◽  
Kaliroi Engel ◽  
Sarah M. Clark ◽  
...  
Keyword(s):  
Zika Virus ◽  
Post Infection ◽  
Late Pregnancy ◽  
Congenital Defects ◽  
Low Grade ◽  
Mrna Levels ◽  
Neurodevelopmental Disease ◽  
Behavioral Monitoring ◽  
In Pregnancy

AbstractThe recent spread of Zika virus (ZIKV) and its association with congenital defects and neurological disorders has created an urgent need to understand the pathogenesis of ZIKV and identify therapeutic strategies that will prevent or eliminate them. The neurodevelopmental defects associated with ZikV infections early in pregnancy are well documented, however the potential defects associated with infections in late pregnancy and perinatal period are less well characterized. Further, the long-term sequelae of these infections are not fully understood. Immunocompetent C57BL/6 mice infected at one day old (P1), which neurodevelopmentally model late pregnancy in humans, develop a transient neurological syndrome including unsteady gait, kinetic tremors, severe ataxia and seizures 10-15 days post-infection (dpi) but symptoms subside after a week, and most animals survive. Despite apparent recovery, MRI of convalescent mice shows reduced cerebellar volume that correlates with altered coordination and motor function as well as hyperactivity and impulsivity. Persistent mRNA levels of pro-inflammatory genes including Cd80, Il-1α, and Ifn-γ together with Cd3, Cd8 and perforin (PrfA), suggested the persistence of a low-grade inflammatory process. Further, the brain parenchyma of convalescent mice harbor multiple small foci with viral antigen, active apoptotic processes in neurons, and cellular infiltrates, surrounded by activated astrocytes and microglia as late as 1-year post-infection. Detection of negative-sense strand viral RNA and replication of virus derived from these convalescent mice by blinded passage in Vero cells confirmed that low levels of live ZikV persist in CNS of convalescent mice life-long. Our studies establish that Zika can establish reservoirs in CNS and suggest that anti-viral treatment that clears virus from the CNS as well as long-term neurological and behavioral monitoring may be needed for patients known to be exposed to ZikV at an early age.Author’s summaryThe congenital brain malformations associated with ZikV infections early in pregnancy are well documented, however whether apparently asymptomatic perinatal exposure could lead to long term sequelae is not fully understood. Using a non-lethal neonatal mouse model, we examine host-pathogen interactions, anatomical changes and behavioral patterns by following survivors of the acute infection for over 1 year. We discover that infectious Zika virus has the potential to remain in the CNS for life, lodged within small foci surrounded by gliosis and infiltrating immune cells that may act to limit the viral spread, but also interfere with healing and contribute to life-long neuropathic and behavioral sequelae. These results suggest that anti-viral treatment and long-term neurological and behavioral monitoring may be indicated for patients known to have been exposed to Zika virus, regardless of neurodevelopmental disease severity.

MiR-493 Induces Cytotoxic Autophagy in Prostate Cancer Cells through Regulation on PHLPP2

2020 ◽  
Vol 21 (14) ◽  
pp. 1451-1456 ◽  
Author(s):  
Jun Deng ◽  
Ming Ma ◽  
Wei Jiang ◽  
Liangliang Zheng ◽  
Suping Cui
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Cell Function ◽  
Mrna Levels ◽  
Prostate Cancer Cells ◽  
Potent Inducer ◽  
Qrt Pcr ◽  
Autophagy Gene ◽  
The Relationship ◽  
Cancer Inhibition

Background: MiR-493 promotes the proliferation of prostate cancer (PC) cells by targeting PHLPP2. We aimed to explore the relationship between miR-493 and autophagy in PC. Methods: qRT-PCR and western blotting were used to determine the mRNA levels and protein expression of miR-493, PHLPP2, autophagy gene BECN1 and ATG7 in PC cells. The autophagy gene expression was determined after PC cells transfected with miR-493 precursor or PHLPP2 precursor. Corresponding changes of autophagy phenotype and PC cell function were also studied. Results: The mRNA levels and protein expression of miR-493, PHLPP2, BECN1 and ATG7 in PC cells were significantly decreased in PC cells. Overexpression of miR-493 or PHLPP2 markedly upregulated the expression levels of BECN1 and ATG7 in PC cells. Overexpression of miR-493 and PHLPP2 markedly promoted autophagy, and inhibited the invasion and cloning formation of PC cells. Conclusion: MiR-493 is a potent inducer of cytotoxic autophagy that leads to prostate cancer inhibition by regulating on PHLPP2.

scholarly journals Cardiac small-conductance calcium-activated potassium channels in health and disease

2021 ◽  
Vol 473 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Xiao-Dong Zhang ◽  
Phung N. Thai ◽  
Deborah K. Lieu ◽  
Nipavan Chiamvimonvat
Keyword(s):  
Ventricular Myocytes ◽  
Pulmonary Veins ◽  
Differential Sensitivity ◽  
Sk Channels ◽  
Sk Channel ◽  
Ventricular Cells ◽  
Intracellular Ca ◽  
Life Threatening ◽  
Health And Disease ◽  
Small Conductance

AbstractSmall-conductance Ca2+-activated K+ (SK, KCa2) channels are encoded by KCNN genes, including KCNN1, 2, and 3. The channels play critical roles in the regulation of cardiac excitability and are gated solely by beat-to-beat changes in intracellular Ca2+. The family of SK channels consists of three members with differential sensitivity to apamin. All three isoforms are expressed in human hearts. Studies over the past two decades have provided evidence to substantiate the pivotal roles of SK channels, not only in healthy heart but also with diseases including atrial fibrillation (AF), ventricular arrhythmia, and heart failure (HF). SK channels are prominently expressed in atrial myocytes and pacemaking cells, compared to ventricular cells. However, the channels are significantly upregulated in ventricular myocytes in HF and pulmonary veins in AF models. Interests in cardiac SK channels are further fueled by recent studies suggesting the possible roles of SK channels in human AF. Therefore, SK channel may represent a novel therapeutic target for atrial arrhythmias. Furthermore, SK channel function is significantly altered by human calmodulin (CaM) mutations, linked to life-threatening arrhythmia syndromes. The current review will summarize recent progress in our understanding of cardiac SK channels and the roles of SK channels in the heart in health and disease.

DIE AUSSCHEIDUNG VON TESTOSTERON UND EPITESTOSTERON BEI FRAUEN AM ENDE DER SCHWANGERSCHAFT

1969 ◽  
Vol 60 (4) ◽  
pp. 579-585
Author(s):  
K. Schollberg ◽  
E. Seiler ◽  
J. Holtorff
Keyword(s):  
Urinary Excretion ◽  
Late Pregnancy ◽  
Mean Values ◽  
Pregnant Females ◽  
Female Foetus ◽  
The Mean ◽  
The Difference ◽  
Normal Women ◽  
In Pregnancy

ABSTRACT The urinary excretion of testosterone and epitestosterone by women in late pregnancy has been studied. The mean values of 22 normal women in pregnancy mens X are 12.9 ± 9.2 μg/24 h in the case of testosterone and 16.1 ± 16.2 μg/24 h in the case of epitestosterone. Both values do not differ significantly from those of non-pregnant females. The excretion values of mothers bearing a male foetus (17.3 ± 8.9 μg/24 h) are higher than those of mothers with a female foetus (6.4 ± 4.8 μg/24 h). The difference is statistically significant with P = 0.01.

Thiazides in pregnancy

1965 ◽  
Vol 3 (3) ◽  
pp. 10-11
Keyword(s):  
Blood Pressure ◽  
Perinatal Mortality ◽  
Thiazide Diuretic ◽  
Late Pregnancy ◽  
Common Complication ◽  
In Pregnancy

Pre-eclampsia is a common complication of late pregnancy and may endanger the life of the mother or her child. The cause is unknown and treatment is aimed at correcting the manifestations of the disease empirically. The signs are hypertension, oedema and proteinuria, and one of these, the oedema, can often be reduced by a thiazide diuretic. In some studies1–3 but not in others4–6 thiazides have also been reported to lower the blood pressure. Proteinuria persists and may worsen7 and the perinatal mortality is not improved8 with thiazide therapy. The placental damage associated with pre-eclampsia and its effects on the foetus are apparently not reversed when the oedema and hypertension are reduced.

miR-26b Regulates Osteoactivin (OA)-Induced Bone Marrow Mesenchymal Cells (BMSCs) Osteogenic Differentiation by Targeting Fms-Like Tyrosine Kinase 3 (FLT3)/AXL

2021 ◽  
Vol 11 (9) ◽  
pp. 1774-1779
Author(s):  
Feng Sun ◽  
Tianwen Huang ◽  
Jianhui Shi ◽  
Tianli Wei ◽  
Haiwei Zhang
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Tyrosine Kinase ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Formation Process ◽  
Mesenchymal Cells ◽  
Mrna Levels ◽  
Qrt Pcr ◽  
Bone Marrow Mesenchymal Cells

Osteoactivin (OA) plays a key role in osteogenic differentiation. miR-26b is elevated in the bone formation process of BMSCs, but whether it is involved in this process is unclear. Bone formation is regulated by FLT3/AXL signaling pathway, which may be a potential target of miR-26b. qRT-PCR detected miR-26b mRNA levels and bone formation-related genes or FLT3/AXL signaling pathway-related genes. Bone formation was analyzed by staining and FLT3/AXL signaling was evaluated along with analysis of miR-26b’s relation with LT3/AXL. miR-26b was significantly elevated in OA-induced bone formation of BMSCs, which can be promoted by miR-26b mimics. When miR-26b was overexpressed, FLT3/AXL signaling pathway was activated. miR-26b can ameliorate Dex-induced osteo-inhibition. miR-26b promotes bone formation of BMSCs by directly targeting FLT3/AXL signaling pathway, suggesting that miR-26b might be a target for inducing osteogenic differentiation.

Fibrin monomer complex in normal pregnant women: a potential thrombotic marker in pregnancy

2007 ◽  
Vol 44 (5) ◽  
pp. 449-454 ◽  
Author(s):  
Hiroaki Onishi ◽  
Kimiko Kaniyu ◽  
Mitsutoshi Iwashita ◽  
Asashi Tanaka ◽  
Takashi Watanabe
Keyword(s):  
Pregnant Women ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
Reference Ranges ◽  
Vein Thrombosis ◽  
Fibrin Monomer ◽  
Potential Marker ◽  
Deep Vein ◽  
Positive Results ◽  
In Pregnancy

Background: Pregnancy represents a major risk factor for deep vein thrombosis (DVT). Most coagulation/fibrinolysis markers currently utilized change during pregnancy, and therefore they cannot accurately evaluate thrombotic events in pregnancy because the rate of false positive results is high. Fibrin monomer complex (FMC) has recently become widely available for diagnosing DVT. The present study examined whether FMC is suitable for evaluating thrombotic status in pregnancy. Methods: Concentrations of FMC and other haemostatic markers were investigated in 87 pregnant women without major complications at early, mid- or late pregnancy. FMC concentrations were also measured in 127 normal non-pregnant women, and in one woman who developed DVT after delivery. Results: In normal pregnant women, FMC concentrations were unchanged during early or mid-pregnancy and slightly elevated during late pregnancy. Concentrations were within reference range in most cases, and none exceeded the cut-off value for DVT. In contrast, thrombin-antithrombin complex (TAT) and D-dimer (DD) concentrations were significantly elevated in late pregnancy, and median values exceeded reference ranges. The DVT case displayed significantly elevated FMC concentrations. Conclusions: Changes in FMC concentrations during normal pregnancy are minimal compared with other haemostatic markers. Because the rate of false positivity is lower, FMC could be a potential marker of thrombotic status in pregnancy rather than TAT and DD.

scholarly journals Effect of lentivirus-mediated growth and differentiation factor-5 transfection on differentiation of rabbit nucleus pulposus mesenchymal stem cells

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Kun Zhu ◽  
Rui Zhao ◽  
Yuchen Ye ◽  
Gang Xu ◽  
Changchun Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nucleus Pulposus ◽  
Lentiviral Vector ◽  
The Other ◽  
Cell Phenotype ◽  
Mrna Levels ◽  
Qrt Pcr ◽  
Differentiation Factor ◽  
Gdf5 Gene

Abstract Background Intervertebral disc degeneration (IDD) is a natural progression of age-related processes. Associated with IDD, degenerative disc disease (DDD) is a pathologic condition implicated as a major cause of chronic lower back pain, which can have a severe impact on the quality of life of patients. As degeneration progression is associated with elevated levels of inflammatory cytokines, enhanced aggrecan and collagen degradation, and changes in the disc cell phenotype. The purpose of this study was to investigate the biological and cytological characteristics of rabbit nucleus pulposus mesenchymal stem cells (NPMSCs)—a key factor in IDD—and to determine the effect of the growth and differentiation factor-5 (GDF5) on the differentiation of rabbit NPMSCs transduced with a lentivirus vector. Methods An in vitro culture model of rabbit NPMSCs was established and NPMSCs were identified by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Subsequently, NPMSCs were randomly divided into three groups: a transfection group (the lentiviral vector carrying GDF5 gene used to transfect NPMSCs); a control virus group (the NPMSCs transfected with an ordinary lentiviral vector); and a normal group (the NPMSCs alone). FCM, qRT-PCR, and western blot (WB) were used to detect the changes in NPMSCs. Results The GDF5-transfected NPMSCs displayed an elongated shape, with decreased cell density, and significantly increased GDF5 positivity rate in the transfected group compared to the other two groups (P < 0.01). The mRNA levels of Krt8, Krt18, and Krt19 in the transfected group were significantly higher in comparison with the other two groups (P < 0.01), and the WB results were consistent with that of qRT-PCR. Conclusions GDF5 could induce the differentiation of NPMSCs. The lentiviral vector carrying the GDF5 gene could be integrated into the chromosome genome of NPMSCs and promoted differentiation of NPMSCs into nucleus pulposus cells. Our findings advance the development of feasible and effective therapies for IDD.

scholarly journals Lactational Anovulation in Mice Results From a Selective Loss of Kisspeptin Input to GnRH Neurons

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 193-203 ◽  
Author(s):  
X. Liu ◽  
R.S.E. Brown ◽  
A.E. Herbison ◽  
D.R. Grattan
Keyword(s):  
Brain Slice ◽  
Third Ventricle ◽  
Late Pregnancy ◽  
Mrna Levels ◽  
Fiber Density ◽  
Selective Loss ◽  
Fold Reduction ◽  
Gnrh Neurons ◽  
Periventricular Area ◽  
Brain Slice Preparation

In mammals, lactation is associated with a period of infertility characterized by the loss of pulsatile secretion of GnRH and cessation of ovulatory cycles. Despite the importance of lactational infertility in determining overall fecundity of a species, the mechanisms by which the suckling stimulus suppresses GnRH secretion remain unclear. Because kisspeptin neurons are critical for fertility, the aim of this study was to test the hypothesis that reduced kisspeptin expression might mediate the lactation-induced suppression of fertility, using mouse models. In the rostral periventricular area of the third ventricle (RP3V), a progressive decrease in RP3V Kiss1 mRNA levels was observed during pregnancy culminating in a 10-fold reduction during lactation compared with diestrous controls. This was associated with approximately 60% reduction in the numbers of kisspeptin-immunoreactive neurons in the RP3V detected during lactation. Similarly, in the arcuate nucleus there was also a significant decrease in Kiss1 mRNA levels during late pregnancy and midlactation, and a notable decrease in kisspeptin fiber density during lactation. The functional characteristics of the RP3V kisspeptin input to GnRH neurons were assessed using electrophysiological approaches in an acute brain slice preparation. Although endogenous RP3V kisspeptin neurons were found to activate GnRH neurons in diestrous mice, this was never observed during lactation. This did not result from an absence of kisspeptin receptors because GnRH neurons responded normally to 100 nM exogenous kisspeptin during lactation. The kisspeptin deficit in lactating mice was selective, because GnRH neurons responded normally to RP3V gamma aminobutryic acid inputs during lactation. These data demonstrate that a selective loss of RP3V kisspeptin inputs to GnRH neurons during lactation is the likely mechanism causing lactational anovulation in the mouse.

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