BackgroundLong non-coding RNAs (lncRNAs) have been reported to modulate cardiovascular diseases, and expression dynamics of lncRNAs in the bloodstream were proposed to be potential biomarkers for clinical diagnosis. However, few cardiovascular diseases-related circulating lncRNAs were identified and their prediction power has not been investigated in depth. Here we report a new circulating lncRNA, atherosclerotic plaque pathogenesis associated transcript (APPAT), and evaluated its role and predicting ability in atherosclerotic development.MethodsAPPAT was analyzed and screened by high-throughput sequencing, and then detected in vitro and in vivo. Immunofluorescence-fluorescence in situ hybridization (IF-FISH) was utilized to explore distribution and subcellular location of APPAT. The expressing alteration of APPAT in samples of healthy and pathological coronary artery was explored further. We also assessed the level of circulating APPAT in blood samples from healthy individuals, and patients with angina pectoris (AP) or myocardial infarction (MI). Additionally, we predicted and validated microRNA targets of APPAT, then showed the expression level of a candidate target which was primarily measured in human VSMCs cell line, coronary artery, and blood samples. Lastly, we examined the potential indicating ability of APPAT for the risk of AP or MI.ResultsAPPAT showed significant reduction in ox-LDL treated human VSMCs in vitro. It enriched in contractile VSMCs of artery tunica media and mainly existed in cytoplasm. Significant down-regulation of APPAT was found in coronary artery samples with severe stenosis. More importantly, we observed decreased expression of APPAT in blood samples accompanying disease progression. ROC and correlation analyses further verified the relatively high predicting ability of APPAT. We also observed the predicted miRNA exhibited opposite expression direction to that of APPAT.ConclusionsThis study revealed that circulating lncRNA-APPAT may perform an important function and have some indicating ability on the development of atherosclerosis.

BackgroundChemerin is highly expressed in the serum, placenta tissue, and umbilical cord blood of diabetic mother; however, the impact of chemerin on cognitive disorders of offspring from mothers with diabetes in pregnancy remains unclear.MethodsA diabetic phenotype in pregnant mice dams was induced by streptozocin (STZ) injection or intraperitoneal injection of chemerin. Behavioral changes in offspring of diabetic dams and nondiabetic controls were assessed, and changes in chemerin, two receptors of chemerin [chemerin receptor 23 (ChemR23) and chemokine (C-C motif) receptor-like 2 (CCRL2)], macrophages, and neurons in the brain tissue were studied to reveal the underlying mechanism of the behavioral changes.ResultsChemerin treatment mimicked the STZ-induced symptom of maternal diabetes in mice along with the altered behavior of offspring in the open field test (OFT) assay. In the exploring process for potential mechanism, the brain tissues of offspring from chemerin-treated dams were observed with an increase level of macrophage infiltration and a decrease number of neuron cells. Moreover, an increased level of NOD-like receptor family pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like (Asc) protein as well as pyroptosis [characterized by increased active caspase-1 content and secretion of cytokines such as interleukin (IL) 1 beta (IL-1β) and IL-18] more activated in macrophages is also observed in the brain of these diabetic dam’s offspring, in the presence of ChemR23. In vitro, it was found that pyroptosis activation was increased in macrophages separated from the abdominal cavity of normal mice, after chemerin treatment. However, depletion of CCRL2 decreased the level of chemerin in the brain tissues of diabetic dams’ offspring; depletion of ChemR23 decreased macrophage pyroptosis, and depletion of either receptor reversed chemerin-mediated neurodevelopmental deficits and cognitive impairment of offspring of diabetic pregnant dams.ConclusionsChemerin induced diabetic pregnant disease and CCRL2 were required to enrich chemerin in the brain of offspring. Aggregation of chemerin could lead to macrophage recruitment, activation of pyroptosis, the release of inflammatory cytokines, a decrease in the number of neurons, and cognitive impairment in offspring in a ChemR23-dependent manner. Targeting CCRL2 and/or ChemR23 could be useful for treating neuropsychological deficits in offspring of dams with diabetes in pregnancy.Electronic supplementary materialThe online version of this article (10.1186/s12974-019-1573-6) contains supplementary material, which is available to authorized users.

The aim of this study is to investigate the association between maternal gestational weight gain (GWG) and preterm birth according to pre-pregnancy body mass index (BMI) and maternal age. We did a cohort, hospital-based study in Quzhou, South China, from 1 Jan 2018 to 30 June 2019. We selected 4274 singleton live births in our analysis, 315 (7.4%) of which were preterm births. In the overall population, excess GWG was significantly associated with a decreased risk of preterm birth compared with adequate GWG (adjusted OR 0.81 [95% CI 0.72–0.91]), and the risk varied by increasing maternal age and pre-pregnancy BMI. Interestingly, underweight women who older than 35 years with excess GWG had significantly increased odds of preterm birth compared with adequate GWG in underweight women aged 20–29 years (2.26 [1.06–4.85]) and normal weight women older than 35 years (2.23 [1.13–4.39]). Additionally, low GWG was positively and significantly associated with preterm birth overall (1.92 [1.47–2.50]). Among normal weight women category, compared with adequate GWG women aged 20–29 years did, those older than 20 years with low GWG, had significantly higher odds of preterm birth, which increased with maternal age (1.80 [1.16–2.79] in 20–29 years, 2.19 [1.23–3.91] in 30–34 years, 3.30 [1.68–6.46] in ≫ 35 years). In conclusion, maternal GWG was significantly associated with the risk of preterm birth, but the risk varied by pre-pregnancy BMI and maternal age.

To reassess the efficacy of levothyroxine on subclinical hypothyroidism (SCH, 4.0 mIU/L ≤ TSH (thyroid stimulating hormone) <10 mIU/L with normal free T4) during pregnancy. 165 levothyroxine-treated pregnant women experiencing SCH were screened. And controls were randomly selected using euthyroidism (EU) women, matched by age, gravidity, and parity in the EU group (n = 660). We evaluated laboratory characteristics and pregnancy outcomes during follow-ups. Compared with the EU group, the SCH group displayed higher inadequate maternal gestational weight gain, premature delivery, low birth weight offspring and infant offspring small for their gestational age. After levothyroxine treatment, the SCH group displayed lower total cholesterol, low-density lipoprotein levels, and higher serum homocysteine levels before delivery. Pregnant women with SCH still exhibit adverse pregnancy outcomes after levothyroxine treatment. Taken together, we believe that besides levothyroxine, vitamin B12 and folic acid could be added to the treatment of pregnant women with SCH. In addition, regular monitoring of blood sugar levels, lipid and homocysteine levels, and intervention gestational weight gain could alleviate the adverse effects of SCH on pregnancy outcomes.