Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage‐associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF‐κB, STATs, and NLRP3/caspase‐1. Notably, miRNAs (eg, miR‐155/‐34a/‐23a), cellular metabolic pathways (eg, α‐KG, HIF‐1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage‐associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage‐associated diseases.

Objective To investigate the volume of intracranial structures in fetuses with congenital heart disease (CHD). Methods

VVI is a novel noninvasive tool for quantitative assessment of regional systolic and diastolic function of the fetal heart. Fetal myocardial velocity, strain, and strain rate measurements can be measured easily and reproducibly. This technique is useful for evaluating cardiac function.

BackgroundCholangiocarcinoma (CCA) is a form of cancer that easily aggress to contiguous structures. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) are increased in majority species of cancers and suppress tumor progression by blocking VEGF/VEGFR2. Apatinib is a highly selective VEGFR2 antagonist which has inhibitive effect on antiapoptotic and cell growth in CCA. While, the effect of apatinib cell migration and invasion in CCA is still unknown.MethodsCCA cell lines QBC939 and TFK-1 were transfected with siKDR to establish the KDR function loss cell model, and recombined human VEGF (rhVEGF) protein was added into the culture medium to enhance the VEGF expression. RT-qPCR and western bloting were used to detect the mRNA and protein expression levels of VEGFR2 to investigate whether it was effectively repressed or activated with rhVEGF or apatinib treatment. Then, MTT, wound healing assay, and transwell matrix assay were applied to measure the effect of apatinib and rhVEGF on cell viability, migration and invasion, respectively.ResultsThe mRNA and protein expressions of VEGFR2 were significantly reduced with KDR RNAi in both QBC939 and TFK-1 cells, and rhVEGF treatment increased these expression levels (p < 0.05). Apatinib dramatically suppressed VEGF-mediated cell migration and invasion at the concentration of 100 nM treatment and significantly decreased the expression of metastasis-associated protein such as Slug, snail and MMP9. Moreover, all of these inhibiting effects of apatinib depended on the VEGFR2 existence. In addition, VEGFR2/RAF/MEK/ERK and PI3K/AKT signal pathways were enhanced by the introduction of rhVEGF, but were dramatically suppressed after the apatinib treatment.ConclusionApatinib inhibit VEGF-mediated cell migration and invasion in CCA cell lines via inhibiting the VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways. It will be a potentially effective targeted drug for CCA.

Objectives: Twin-twin transfusion syndrome (TTTS) is a complex disorder with altered cardiovascular loading conditions that affects both donors and recipients. Myocardial tissue deformation analysis using vector velocity imaging is an angle-independent, speckle-tracking technique which can assess myocardial mechanics and may provide insight into cardiac dysfunction in TTTS. Methods: Digital dynamic two-dimensional four-chamber views were interrogated offline. Images were acquired utilizing standard video frame rates (30 frames/s). The global longitudinal strain, systolic strain rate, and diastolic strain rate were measured in the left (LV) and right ventricles (RV) of 25 fetal pairs with TTTS and compared to 25 gestational age-matched normal controls. Pulsatility indices for the umbilical artery and middle cerebral artery were measured. Results: The gestational age at evaluation was 20.5 ± 1.3 weeks. The donor LV systolic strain rate was higher, while the donor RV diastolic strain rate was significantly lower, than control values. The recipient longitudinal strain, systolic strain rate, and diastolic strain rate were significantly lower for both LV and RV in comparison to controls. The donor umbilical artery pulsatility index was higher than control values (1.92 ± 0.45 vs. 1.41 ± 0.25, p < 0.001), while the donor middle cerebral artery pulsatility index was lower (1.46 ± 0.28 vs. 1.87 ± 0.21). Recipient umbilical artery and middle cerebral artery pulsatility indices were no different than control values. Conclusions: In TTTS, both the donor and the recipient exhibit abnormalities of myocardial tissue deformation with ventricle-specific changes evident based on loading conditions. Donor LV systolic function is hyperdynamic due to hypovolemia and selective ejection into a low-resistance cerebrovascular circuit while the donor RV selectively ejects into a high-resistance placental circuit. Recipient RV and LV are both globally depressed with systolic and diastolic dysfunction. Further prospective validation of our findings using high frame rate analysis is indicated.

The aim was to investigate the impact of maternal hyperoxygenation (HO) on cardiac dimensions in fetuses with isolated Coarctation (CoA). Fetal echocardiography was performed serially in 48 fetuses with CoA and gestation age matched normal fetues. The Z-scores for the mitral valve (MV), tricuspid valve (TV), aortic valve (AV), ascending aorta (AAo), isthmus, pulmonary valve (PV), main pulmonary artery (MPA), and descending aorta (DAo) were measured and compared among normal fetuses, CoA fetuses with oxygen and CoA fetuses with air. In the group with oxygen, 6 L/min oxygen was administered to the mother using a face mask. Regression analyses were performed to identify potential factors for HO outcome. The left heart dimension Z-scores increased gradually during HO therapy periods, especially at 4 weeks after oxygen therapy (P < 0.05). As for the case group with air, the left heart dimension remained unchanged. The duration of HO was associated with aortic arch Z-scores (adjusted R2 = 0.199, 0.60 for AAO and isthmus, respectively). Sustained maternal middle-flow oxygenation can be safely used to improve left heart dimensions in fetuses with isolated CoA. The duration of HO were associated with treatment outcome. These findings may provide useful information for developing novel treatment strategies.

ObjectivesThe velocity vector imaging (VVI) technique is useful to assess regional myocardial mechanics. The aim of this study was to evaluate the usefulness of this technology in assessing regional right ventricular longitudinal functions in the fetus and to establish a nomogram of the right ventricle (RV). MethodsWe studied 170 healthy fetuses that were divided into five groups based on gestational age. Dynamic digital images of four chambers were collected and analyzed off-line. The longitudinal VVI parameters were calculated in the right free wall and ventricular septum, respectively.Results A total of 151 out of 170 fetuses (89%) were successfully analyzed using VVI, with good interand intra-observer agreements. Normal values for velocity, strain, and strain rate were established. The tissue velocity gradually decreased from basal to apical segment (P < 0.05), whereas strain and strain rate remained stable. The tissue velocity increased with gestational age (P < 0.05), whereas strain and strain rate were stable (P > 0.05). ConclusionFetal myocardial velocity, strain, and strain rate measurements are easy to obtain and are reproducible. From mid-to-late gestation, the longitudinal tissue velocity of the RV increases with gestational age, whereas strain and strain rate remain stable. These results indicate that myocardial contractility is established in mid-gestation and remains constant throughout gestation.

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