Explore the vast range of titles available.

Background To evaluate the differences in pregnancy outcomes between assisted reproductive technology (ART) patients and natural pregnant women in Shanghai, China in the past 6 years objectively. And to assess the feasibility of the research method of registry-database linkage in mainland China. Methods This retrospective study was conducted using registry-database linkage. A total of 8102 pregnancies with ART and 8096 parturients with spontaneous conception (SC) from 10 reproductive centers and 111 hospitals composed our retrospective study. The primary outcomes were the rates of obstetric complications (pregnancy-induced hypertention [PIH], gestational diabetes mellitus [GDM], placenta previa, mode of delivery, preterm birth [PTB], low birth weight [LBW], and macrosomia). The prenatal outcomes were compared between ART and SC parturients, frozen-thawed embryo transfer (FET) and fresh embryo transfer, and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). We calculated odds ratios (ORs) and 95% confidence intervals (CIs). Results The final matching rate of the target population was 92% by using registry linkage. ART resulted in a higher rate of multiple birth, PTB, LBW, cesarean section, placenta previa and GDM compared with SC in the singleton cohort. In ART patients, pregnant women with FET had a significantly higher risk of PIH than those with fresh embryo transfer (14.1% Vs 9.3%, AOR1.528, 95% CI 1.303–1.793), but there was no difference between IVF and ICSI. FET is also related to the severity of PIH. Conclusions ART increased the rate of complications during pregnancy, the risk and severity of PIH in patients with FET was higher than that in patients with fresh embryo transfer. The registry-database linkage study is an objective and feasible research method in mainland China.

Background/ObjectivesThe results linking body iron stores to the risk of gestational diabetes mellitus (GDM) are conflicting. We aimed to measure the serum ferritin level of women in early pregnancy and evaluate the risk of GDM in a Chinese urban population.Subjects/MethodsIn total, 851 pregnant women between 10 and 20 weeks of gestation took part in the prospective, observational study conducted. The women were divided into four groups by quartiles of serum ferritin levels (Q1–4). Their blood samples were collected and assayed for several biochemical variables at the beginning of the study, and the women were followed up with a 75-g oral glucose tolerance test at 24–28 weeks of gestation.ResultsThe participants had an average serum ferritin concentration of 65.67 μg/L. GDM prevalence within each serum ferritin quartile was 9.4%, 14.6%, 18.8% and 19.3%, respectively, (P = 0.016). The odds ratio for GDM in the ferritin Q2–4 was 1.64 (CI: 0.90–2.99), 2.23 (CI: 1.26–3.96) and 2.31 (CI: 1.30–4.10), compared with Q1, respectively. This association persisted after adjusting for potential confounders factors. In addition, in Q4, pregnant women with a pre-pregnancy body mass index ≥24 kg/m2, maternal age ≤35 years old or haemoglobin≥ 110 g/L did have an increased risk of developing GDM.ConclusionsElevated serum ferritin concentrations in early gestation are associated with an increased risk of GDM, especially in pregnant women who have a high baseline iron storage status with no anaemia or who are overweight/obese. Individual iron supplementation should be considered to minimize the risk of GDM.

Mesenchymal stem cell (MSC) transplantation reduces the neurological impairment caused by hypoxic-ischemic brain damage (HIBD) via immunomodulation. In the current study, we found that MSC transplantation improved learning and memory function and enhanced long-term potentiation in neonatal rats subjected to HIBD and the amount of IL-6 released from MSCs was far greater than that of other cytokines. However, the neuroprotective effect of MSCs infected with siIL-6-transduced recombinant lentivirus (siIL-6 MSCs) was significantly weakened in the behavioural tests and electrophysiological analysis. Meanwhile, the hippocampal IL-6 levels were decreased following siIL-6 MSC transplantation. In vitro , the levels of IL-6 release and the levels of IL-6R and STAT3 expression were increased in both primary neurons and astrocytes subjected to oxygen and glucose deprivation (OGD) following MSCs co-culture. The anti-apoptotic protein Bcl-2 was upregulated and the pro-apoptotic protein Bax was downregulated in OGD-injured astrocytes co-cultured with MSCs. However, the siIL-6 MSCs suppressed ratio of Bcl-2/Bax in the injured astrocytes and induced apoptosis number of the injured astrocytes. Taken together, these data suggest that the neuroprotective effect of MSC transplantation in neonatal HIBD rats is partly mediated by IL-6 to enhance anti-apoptosis of injured astrocytes via the IL-6/STAT3 signaling pathway.

Background There is growing interest regarding vitamin D and its potential role in gestational diabetes mellitus (GDM). We aimed to assess maternal vitamin D status in early pregnancy and its relationships with the risk of GDM in a Chinese population in Shanghai. Methods The retrospective cohort study included a total of 7816 pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) during 24–28 weeks of gestation. Participants’ demographic information including maternal age, prepregnancy body mass index (BMI), gestational age, parity, season of blood collection, serum 25-hydroxy vitamin D [25(OH)D] data and other blood biomarker data at 6 to 14 weeks of gestation were retrospectivly extracted from the medical records in the hospital information system. Results In the cohort, the prevalence of GDM was 8.6% and the prevalence of vitamin D deficiency and insufficiency in early pregnancy was 53.1 and 38.5%, respectively. The mean value of the serum 25(OH)D concentration was 19.6±7.5 ng/mL. The restricted cubic splines model showed an inverted J-shaped relationship in which the risk of GDM decreased when the 25(OH)D concentrations were ≥ 20 ng/mL. Logistic model analysis showed that 25(OH)D concentrations ≥ 30 ng/mL significantly decreased the risk of GDM (odds ratio = 0.63, 95% confidence interval: 0.45-0.89; P = 0.010) compared with 25(OH)D concentrations < 20 ng/ml. Conclusions In early pregnancy, vitamin D deficiency and insufficiency were very common, and a high level of vitamin D showed protective effects against the incidence risk of GDM.

Background. Increasing evidence has revealed that mesenchymal stromal cell (MSC) transplantation alleviates hypoxic-ischemic brain damage (HIBD) induced neurological impairments via immunomodulating astrocyte antiapoptosis effects. However, it remains unclear whether MSCs regulate neuron autophagy following HIBD. Results. In the present study, MSC transplantation effectively ameliorated learning-memory function and suppressed stress-induced hippocampal neuron autophagy in HIBD rats. Moreover, the suppressive effects of MSCs on autophagy were significantly weakened following endogenous IL-6 silencing in MSCs. Suppressing IL-6 expression also significantly increased p-AMPK protein expression and decreased p-mTOR protein expression in injured hippocampal neurons. Conclusion. Endogenous IL-6 in MSCs may reduce autophagy in hippocampal neurons partly through the AMPK/mTOR pathway.

In mammals, the tachykinin 3 (TAC3)/tachykinin receptor 3 (TACR3) systems have been confirmed to play an important role in the regulation of puberty onset. Using grass carp pituitary cells as the model, our recent study found that the TAC3 gene products could significantly induce somatolactin α (SLα) synthesis and secretion via TACR3 activation. In the present study, we seek to examine if pituitary TACR3 can serve as a regulatory target and contribute to TAC3 interactions with other SLα regulators. Firstly, grass carp TACR3 was cloned and tissue distribution showed that it could be highly detected in grass carp pituitary. Using HEK293 cells as the model, functional expression also revealed that grass carp TACR3 exhibited ligand binding selectivity and post-receptor signaling highly comparable to its mammalian counterpart. Using grass carp pituitary cells as the model, TACR3 mRNA expression could be stimulated by insulin-like growth factor (IGF)-I and -II via the IGF-I receptor coupled to phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. Interestingly, IGF-I/-II cotreatment could also significantly enhance TAC3-induced SLα mRNA expression and the potentiating effect was dependent on TACR3 expression and activation of adenylate cyclase (AC)/cAMP/protein kinase A (PKA), phospholipase C (PLC)/inositol 1,4,5-triphosphate (IP3)/protein kinase C (PKC), and Ca2+/calmodulin (CaM)/calmodulin-dependent protein kinase II (CaMK-II) cascades. Besides, IGF-I-induced Akt phosphorylation but not MEK, extracellular signal-regulated kinase (ERK1/2), and P38MAPK phosphorylation was notably enhanced by TACR3 activation. These results, as a whole, suggest that the potentiating effect of IGFs on TAC3 gene products-induced SLα mRNA expression was mediated by TACR3 upregulation and functional crosstalk of post-receptor signaling in the pituitary.

Disclosure: C. Ye: None. X. Qin: None. M. He: None. A.O. Wong: None. Phoenixin (PNX), a novel peptide identified by bioinformatics, is known to have pleiotropic functions mediated by its receptor GPR173. At present, very little is known for PNX regulation and the intracellular signaling for PNX expression is still unclear. Recently, PNX and GPR173 were cloned in grass carp and found to be co-expressed in carp lactotrophs. In carp pituitary cells, PNX was also confirmed to be a novel autocrine/paracrine factor maintaining/stimulating prolactin (PRL) synthesis & secretion. To unveil the functional role of PNX in PRL regulation, a systematic screening of >40 neuroendocrine factors/local growth factors was conducted in the same cell model to look for regulators with modulatory functions for both PNX and PRL in carp pituitary. Based on our study, IGF-I & -II were shown to elevate PNX mRNA level with parallel rise in PRL gene expression in carp pituitary cells whereas the opposite was true for the functional agonist of LH, namely hCG. In parallel experiment, PRL mRNA expression induced by IGF-I was negated by removing endogenous PNX using immunoneutralization with PNX antiserum. Besides, hCG inhibition on PNX & PRL gene expression could be mimicked by parallel treatment of LH but not FSH, whereas removal of endogenous LH by LH antiserum immunoneutralization could lead to the opposite effects. Of note, hCG co-treatment not only attenuated the PNX and PRL responses induced by IGF-I but also triggered notable suppression of IGF-I receptor (IGF1R) gene expression at pituitary cell level. In our study, IGF1R & insulin receptor (InsR) expressed in carp pituitary cells were both activated by IGF-I treatment, but IGF-I induced PNX and PRL mRNA expression could be blocked only by the inactivators for IGF1R but not InsR. Using a pharmacological approach, the gene expression of PNX and PRL induced by IGF-I was confirmed to be mediated through the PI3K/Akt and MEK1/2/ERK1/2 but not P38MAPK pathways. Our findings, as a whole, suggest that (i) IGF signals can induce PRL gene expression in carp pituitary via IGF1R coupled to PI3K/Akt & MAPK cascades and this stimulatory effect is mediated via local production of PNX, and (ii) LH released in the pituitary can act locally to inhibit both basal & IGF-induced PRL expression and these inhibitory actions are mediated by blocking pituitary expression of PNX & IGF1R. Presentation: Friday, June 16, 2023

In our previous study, NKB/NK3R system has been shown to act at the pituitary level to up-regulate SLα synthesis and secretion in grass carp. However, whether NK3R expression can serve as a regulatory target at the pituitary level and contribute to NKB interactions with other SLα regulators is still unclear. In current study, using grass carp pituitary cells as a model, we have a novel finding that co-treatment of SLα/SLβ with carp TAC3 gene products, could induce a noticeable enhancement in SLα mRNA expression and these potentiating effects occurred with a parallel rise in NK3R transcript level after SLα/SLβ treatment. Interestingly, the stimulatory effects of SLα/SLβ on NK3R gene expression could be further potentiated by co-treatment with IGF-I/-II and simultaneous exposure of carp pituitary cells to SLα/SLβ and IGF-I/-II in the presence of TAC3 gene products was found to markedly elevated SLα mRNA expression (20 fold increase) and this synergistic stimulation was mediated by cAMP/PKA-, PLC/PKC- and Ca 2+ -dependent cascades functionally coupled with NK3R activation. These findings suggest that local release of SLα via functional interactions with IGF-I/-II and TAC3/NK3R system may constitute a potent stimulatory signal for SLα gene expression in the carp pituitary via up-regulation of NK3R expression.

It has previously been reported that the influence of vitamin D on the metabolism of calcium and phosphorus is associated with diabetes, cardiovascular disease, Alzheimer's disease, cancer and other systemic diseases, and is considered an important indicator of general health. The present study was conducted to determine the effect of various doses of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation and the levels of oxidative stress of pregnant women with gestational diabetes mellitus (GDM). The present randomized, double-blind placebo-controlled clinical trial was conducted on 133 pregnant women with GDM during weeks 24-28 of pregnancy. The patients were randomly divided into four groups. The control group (n=20) received a placebo (sucrose; one granule/day), the low dosage group (n=38) received the daily recommended intake of 200 IU vitamin D (calciferol) daily, the medium dosage group (n=38) received 50,000 IU monthly (2,000 IU daily for 25 days) and the high dosage group (n=37) received 50,000 IU every 2 weeks (4,000 IU daily for 12.5 days). The general characteristics and dietary intakes of the patients with GDM were similar between each group. Using ELISA kits, it was determined that insulin, homeostatic model assessment-insulin resistance and total cholesterol were significantly reduced by high dosage vitamin D supplementation (P<0.05). Total antioxidant capacity and total glutathione levels were significantly elevated as a result of high dosage vitamin D supplementation (P<0.01). In conclusion, high-dose vitamin D supplementation (50,000 IU every 2 weeks) significantly improved insulin resistance in pregnant women with GDM.

Disclosure: F. Jin: None. X. Qin: None. C. Ye: None. M. He: None. A.O. Wong: None. Liver-expressed antimicrobial peptide 2 (LEAP2) is a peptide highly expressed in the liver and its secretion induced by bacterial infection constitutes an integral component of innate immunity in vertebrate species. Recently, LEAP2 has been confirmed to be the endogenous antagonist of the feeding regulator ghrelin, implying that the peptide may play a role in appetite control and energy homeostasis. However, whether LEAP2 can be regulated by metabolic/endocrine signals is still unclear and the signal transduction involved is totally unknown. Using goldfish as a model, three isoforms of LEAP2, namely LEAP2a, 2b & 2c, have been cloned and phylogenetic analysis confirmed that they could be clustered into the clade of fish LEAP2. Comparative synteny also revealed that the three isoforms were derived from separated genes with similar structural organization but located in different chromosomes of goldfish genome. The a.a. sequences and 3D protein structure of LEAP2a-c were found to be highly comparable with LEAP2 of other vertebrates and tissue expression profiling by RT-PCR also showed that they were expressed at high levels in the liver but to a lower extent in other tissues. As members of antimicrobial peptides, goldfish LEAP2a-c not only could exhibit antimicrobial activity against Staphylococcus epidermidis but also play important role in fish innate immunity, which is evidenced by their transcript expression induced by LPS & cytokines at hepatic level as well as in immune tissues in goldfish naturally infected with Aeromonas hydrophila. In goldfish liver cells, transcript expression of LEAP2a-c could be up-regulated in a time- and dose-dependent manner by IGF-I, IGF-II and insulin. Using a pharmacological approach, the stimulatory effects of IGF-I/-II and insulin on the three isoforms of LEAP2 were confirmed to be mediated by IGF-I receptor (IGF1R) but not insulin receptor activation. Furthermore, the PI3K/Akt, MEK/ERK and P38 MAPK pathways were shown to be involved in IGF-I induced LEAP2a-c gene expression. Our findings for the first time demonstrate that the endocrine signals targeting the liver (insulin) or produced locally within the liver (IGF-I & -II) can play a role in regulating LEAP2 expression at the hepatic level, which may shed light on a novel aspect of the functional crosstalk between innate immunity and feeding control/energy balance in fish model. Presentation: Saturday, June 17, 2023