Chromosome instability functions as a potential therapeutic reference by enhancing chemosensitivity to BCL-XL inhibitors in colorectal carcinoma.

Chromosome instability (CIN) and subsequent aneuploidy are prevalent in various human malignancies, influencing tumor progression such as metastases and relapses. Extensive studies demonstrate the development of chemoresistance in high-CIN tumors, which poses significant therapeutic challenges. Given the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma (CRC), here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC cells. By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC. Subsequent analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these drugs. We further revealed the critical role of BCL-XL in the viability of high-CIN CRC cells. In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.

MiR-155-5p improves the insulin sensitivity of trophoblasts by targeting CEBPB in gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication featuring impaired insulin sensitivity. MiR-155-5p is associated with various metabolic diseases. However, its specific role in GDM remains unclear. CCAAT enhancer binding protein beta (CEBPB), a critical role in regulating glucolipid metabolism, has been identified as a potential target of miR-155-5p. This study aims to investigate the impact of miR-155-5p and CEBPB on insulin sensitivity of trophoblasts in GDM. METHODS: Placental tissues were obtained from GDM and normal pregnant women; miR-155-5p expression was then evaluated by RT‒qPCR and CEBPB expression by western blot and immunohistochemical staining. To investigate the impact of miR-155-5p on insulin sensitivity and CEBPB expression, HTR-8/SVneo cells were transfected with either miR-155-5p mimic or inhibitor under basal and insulin-stimulated conditions. Cellular glucose uptake consumption was quantified using a glucose assay kit. Furthermore, the targeting relationship between miR-155-5p and CEBPB was validated using a dual luciferase reporter assay. RESULTS: Reduced miR-155-5p expression and elevated CEBPB expression were observed in GDM placentas and high glucose treated HTR8/SVneo cells. The overexpression of miR-155-5p significantly enhanced insulin signaling and glucose uptake in trophoblasts. Conversely, inhibiting miR-155-5p induced the opposite effects. Additionally, CEBPB was directly targeted and negatively regulated by miR-155-5p in HTR8/SVneo cells. Silencing CEBPB effectively restored the inhibitory effect of miR-155-5p downregulation on insulin sensitivity in trophoblasts. DISCUSSION: These findings suggest that miR-155-5p could enhance insulin sensitivity in trophoblasts by targeting CEBPB, highlighting the potential of miR-155-5p as a therapeutic target for improving the intrauterine hyperglycemic environment in GDM.

Analysis, validation, and discussion of key genes in placenta of patients with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common complication during pregnancy, which can have harmful health consequences for both the mother and the fetus. Given the placenta's crucial role as an endocrine organ during pregnancy, exploring and validating key genes in the placenta hold significant potential in the realm of GDM prevention and treatment. In this study, differentially expressed genes (DEGs) were identified from two databases, GSE70493 and PRJNA646212, and verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in placenta tissues. DEGs expression was detected in normal or high-glucose-treated HTR8/SVneo cells. We also investigated the relationship between DEGs and glucose levels in GDM patients. By selecting the intersection of the two databases, we screened 20 DEGs, which were validated in GDM patients. We observed an up-regulation of SLAMF, ALDH1A2, and CHI3L2, and a down-regulation of HLA-E, MYH11, HLA-DRB5, ITGAX, GZMB, NAIP, TMEM74B, RANBP3L, PAEP, WT-1, and CEP170. We conducted further investigations into the expression of DEGs in HTR8/SVneo cells exposed to high glucose, revealing a significant upregulation in the expression of SERPINA3, while the expressions of HLA-E, BCL6, NAIP, PAEP, MUC16, WT-1, and CEP170 were decreased. Moreover, some DEGs were confirmed to have a positive or negative correlation with blood glucose levels of GDM patients through correlation analysis. The identified DEGs are anticipated to exert potential implications in the prevention and management of GDM, thereby offering potential benefits for improving pregnancy outcomes and long-term prognosis of fetuses among individuals affected by GDM.

Long-term outcomes of offspring from multiple gestations: a two-sample Mendelian randomization study on multi-system diseases using UK Biobank and FinnGen databases.

BACKGROUND: Assisted reproductive technologies (ART) have increased the incidence of multiple births, which can have a negative impact on maternal and offspring health. The study aimed to investigate the association between genetically predicted multiple birth and the risk of 42 common diseases of the nervous, psychiatric, cardiovascular, respiratory, digestive, and endocrine systems. METHODS: The study utilized two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between genetically predicted multiple birth and the genetically predicted risk of diseases. The study used the FinnGen and UK Biobank datasets for analysis. RESULTS: The study found no significant causal relationship between multiple birth and psychiatric disorders. However, the lower limits of the 95% confidence intervals for bipolar affective disorder and anxiety disorders were not robust, indicating a need for further investigation. The study found that multiple birth may be a strong risk factor for infantile cerebral palsy, and caution is necessary in both natural and ART multiple births. The study revealed a potential causal relationship between multiple birth and coronary heart disease, ischemic heart disease, and deep vein thrombosis, which may be related to abnormal intrauterine environments in multiple pregnancies. Surprisingly, multiple birth appears to have a protective effect against some respiratory diseases, such as chronic obstructive pulmonary disease and asthma. CONCLUSIONS: The study highlights the need for caution regarding the risk of infantile cerebral palsy, cardiovascular diseases, and psychiatric disorders in multiple birth. Our study can lead to the development of preventive strategies and improved clinical management for affected infants.

Regulatory mechanisms underlying endoplasmic reticulum stress involvement in the development of gestational diabetes mellitus entail the CHOP-PPARα-NF-κB pathway.

OBJECTIVE: We investigated the proinflammatory functions of endoplasmic reticulum stress and peroxisome proliferator-activated receptor α (PPARα) in the development of gestational diabetes mellitus (GDM) and their relationship in regulating inflammation in GDM. METHODS: This study was performed on placentas of normal pregnant women, women with GDM, and HTR8 cells. Transmission electron microscopy, immunohistochemistry, Western blot analysis, and RT-PCR were performed to analyze ERS and PPARα expression on both normal and GDM pregnancy placentas. ELISA was performed to analyze inflammatory biomarkers. To generate models of the GDM-like state, placentas of normal pregnancy were treated with LPS and polyinosinic-polycytidylic acid (poly [I:C]). TG, CHOP plasmid, and CHOP siRNA were assessed as to their regulation of HTR8 cells to discern the relationship between ERS and PPARα in regulating the inflammation associated with GDM. RESULTS: ERS was elevated in GDM placentas, induced the secretion of IL-6 and TNF-α, and attenuated the expression of GLUT-4. PPARα was diminished in GDM placentas and inhibited the inflammatory responses via the NF-κB nuclear-transport process. 4-PBA reduced CHOP and augmented PPARα, and it decreased IL-6 and TNF-α in our GDM-like explant. However, with both 4-PBA and MK886 treatment, we noted no significant difference in CHOP expression. The level of PPARα was reduced, and that of NF-κB p65 in the nucleus was elevated with TG treatment in the HTR8/Svneo. Knockdown of CHOP increased PPARα and reduced NF-κB p65, while expression of PPARα declined, and that of NF-κB p65 rose with the application of CHOP when HTR8 cells were treated with TG. CONCLUSIONS: ERS contributes to the pathophysiology of GDM in pregnancy via the CHOP-PPARα-NF-κB-signalling pathway by inducing aberrant activation of inflammation and insulin resistance.

LncRNA HCG27 Promotes Glucose Uptake Ability of HUVECs by MiR-378a-3p/MAPK1 Pathway.

OBJECTIVE: Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. LncRNA HLA complex group 27 (HCG27) plays a crucial role in various metabolic diseases. However, the relationship between lncRNA HCG27 and GDM is not clear. This study aimed to verify a competing endogenous RNA (ceRNA) interaction regulation axis of miR-378a-3p/mitogen-activated protein kinase 1 (MAPK1) regulated by HCG27 in GDM. METHODS: LncRNA HCG27 and miR-378a-3p were detected by RT-qPCR. The expression of MAPK1 in umbilical vein endothelial cells (HUVECs) was detected by RT-qPCR and that in the placenta by Western blotting. To explore the relationship among lncRNA HCG27, miR-378a-3p, MAPK1 and the glucose uptake ability of HUVECs, vector HCG27, si-HCG27, miR-378a-3p mimic and inhibitor were transfected to achieve overexpression and inhibition of HCG27 or miR-378a-3p. The interaction between miR-378a-3p and lncRNA HCG27 or MAPK1 was confirmed by the dual-luciferase reporter assay. Besides, glucose consumption by HUVECs was detected by the glucose assay kit. RESULTS: HCG27 expression was significantly decreased in both the placenta and primary umbilical vein endothelial cells, while the expression of miR-378a-3p was significantly increased in GDM tissues, and the expression of MAPK1 was decreased in GDM tissues. This ceRNA interaction regulation axis was proved to affect the glucose uptake function of HUVECs. The transfection of si-HCG27 could significantly reduce the expression of the MAPK1 protein. If the MAPK1 overexpression plasmid was transfected simultaneously with si-HCG27 transfection, the reduced glucose uptake in HUVECs resulting from the decrease in lncRNA HCG27 was reversed. MiR-378a-3p mimic can significantly reduce the mRNA expression of MAPK1 in HUVECs, whereas miR-378a-3p inhibitor can significantly increase the mRNA expression of MAPK1. The inhibition of miR-378a-3p could restore the decreased glucose uptake of HUVECs treated with si-HCG27. Besides, overexpression of lncRNA HCG27 could restore the glucose uptake ability of the palmitic acid-induced insulin resistance model of HUVECs to normal. CONCLUSION: LncRNA HCG27 promotes glucose uptake of HUVECs by miR-378a-3p/MAPK1 pathway, which may provide potential therapeutic targets for GDM. Besides, the fetal umbilical cord blood and umbilical vein endothelial cells collected from pregnant women with GDM after delivery could be used to detect the presence of adverse molecular markers of metabolic memory, so as to provide guidance for predicting the risk of cardiovascular diseases and health screening of offspring.

DHA supplementation and pregnancy complications.

Docosahexaenoic acid (DHA) supplementation is recommended for women during pregnancy because of its neurological, visual, and cognitive effects. Previous studies have suggested that DHA supplementation during pregnancy may prevent and treat certain pregnancy complications. However, there are contradictions in the current related studies, and the specific mechanism by which DHA acts remains unclear. This review summarizes the research on the relationship between DHA intake during pregnancy and preeclampsia, gestational diabetes mellitus, preterm birth, intrauterine growth restriction, and postpartum depression. Furthermore, we explore the impact of DHA intake during pregnancy on the prediction, prevention, and treatment of pregnancy complications as well as its impact on offspring neurodevelopment. Our results suggest that there is limited and controversial evidence for the protective effect of DHA intake on pregnancy complications, with the exception of preterm birth and gestational diabetes mellitus. However, additional DHA supplementation may improve long-term neurodevelopmental outcomes in the offspring of women with pregnancy complications.

Simulation Study on the Optimisation of Replenishment of Landscape Water with Reclaimed Water Based on Transparency.

Water-scarce cities have fewer surface water (SW) resources available for ecological use, causing landscape water to deteriorate due to water shortage and fail to perform their intended landscape functions. As a result, many cities use reclaimed water (RW) to replenish them. However, this could cause concern among the people, as RW usually has higher nutrient concentrations, which may stimulate algae growth and deteriorate the aesthetic senses of the receiving water bodies. In order to assess the feasibility of using RW for this purpose, this study used Xingqing Lake in Northwest China as insight into the effect of RW replenishment on the visual landscape quality of urban landscape water. Water transparency (measured by SD) is used as an intuitive indicator to reflect the comprehensive influence of suspended solids and algae growth on the water's aesthetic quality. Scenario analyses were carried out after calibrating and validating one-year data in MIKE 3 software with both SD and algae growth calculations, and the results showed that the low concentration of suspended matter in RW could compensate for the decrease in SD due to algal blooms caused by high concentrations of nitrogen and phosphorus, and the effect on SD is especially pronounced under conditions that are not conducive to algal growth, such as good flow conditions and low temperature. In addition, to meet a SD ≥ 70 mm, the total water inflow required can be significantly reduced with the optimal application of RW. It is also indicated that partial or complete utilization of RW to replace SW for replenishing the landscape water could be feasible from the viewpoint of landscape quality, at least for the landscape water investigated in this study. This can provide a method for the improvement to urban water management practices by using RW for replenishment in water-scarce cities.

The role of chemerin in the regulation of cGAS-STING pathway in gestational diabetes mellitus placenta.

Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide-bond A oxidoreductase-like protein (DsbA-L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and its mechanisms of action in the context of GDM. The present study aims to investigate the underlying mechanism of cGAS-STING pathway and its regulatory relationship with chemerin in GDM. A total of 50 participants, including 25 cases of GDM patients and 25 pregnant women with normal glucose tolerance, were enrolled, and their placenta tissues at term labor were collected. Besides, an insulin resistance cell model was established on the human trophoblastic cell line to explore the molecular mechanism of chemerin on cGAS-STING pathway. Results showed that there were mitochondrial pathological changes in GDM placenta, accompanied by the decreased expression of DsbA-L, increased level of chemerin, and the activation of cGAS-STING pathway. In the insulin resistant cell model, overexpression of chemerin upregulated protein expression of DsbA-L, and recombinant chemerin presented time-dependent inhibition on the cGAS-STING pathway, but this effect was not dependent on DsbA-L. In conclusion, elevated chemerin is probably a protective mechanism, which may be a potential therapeutic strategy for GDM.

Low-dose asprin use during pregnancy may be a potential risk for postpartum hemorrhage and increased blood loss: a systematic review and meta-analysis.

OBJECTIVE: The association between aspirin use during pregnancy and the risk of postpartum hemorrhage remains unclear. This study aimed to explore the incidence of postpartum hemorrhage and the amount of postpartum blood loss among women who used aspirin during pregnancy. DATA SOURCES: From inception to October 2022, this study searched the following databases: MEDLINE, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials. STUDY ELIGIBILITY CRITERIA: Studies comparing pregnancy outcomes that covered the incidence of postpartum hemorrhage or the amount of postpartum blood loss in pregnancies with aspirin vs placebo (or no aspirin) were included. METHODS: Reviewers separately ascertained studies, obtained data, and gauged study quality. The meta-analysis was conducted using a random effects model owing to the probable heterogeneity of the included studies. The rates of postpartum hemorrhage or the mean amounts of postpartum blood loss were compared, and the odds ratios or mean differences with 95% confidence intervals were estimated. Of note, 2 parts performed both a pooled analysis of randomized controlled trials and cohort studies and a separate analysis of randomized controlled trials. RESULTS: Overall, 21 studies with 373,926 women were included in the postpartum hemorrhage part, and 7 studies with 10,163 women were included in the postpartum blood loss part. The results suggested that aspirin (dose 60-150mg a day) use during pregnancy was associated with an increased incidence of postpartum hemorrhage (odds ratio, 1.20; 95% confidence interval, 1.07-1.34). When only randomized controlled trials were retained, the results remained significant (odds ratio, 1.12; 95% confidence interval, 1.00-1.25). In the second part, higher total blood loss after delivery was obtained (mean difference, 12.85 mL; 95% confidence interval, 3.28-22.42), and the result was unaltered when cohort studies were eliminated (mean difference, 13.72 mL; 95% confidence interval, 4.63-22.81). The conclusions are more likely to be obtained in developed countries. CONCLUSION: Low-dose aspirin use during pregnancy is a potential risk of postpartum hemorrhage and does slightly increase the amount of postpartum blood loss. Without denying the combined value of aspirin, our conclusions raised an alarm for clinicians about postpartum hemorrhage in women using aspirin during pregnancy.

Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

The spatial-temporal evolution mechanism of PM2.5 concentration based on China's climate zoning.

Increasing attention has been given to the impact of PM2.5 concentration on human health. Exploring the influential factors of PM2.5 is conducive to improving air quality. Most existing studies explore the factors that influence the PM2.5 concentration from the perspective of cities or urban agglomerations, while few studies are conducted from the perspective of climate zones. We used the standard deviation ellipse and spatial autocorrelation analysis to explore the spatial-temporal evolution of the PM2.5 concentration in different climate zones in China during 2000-2018. We used differentiated EKC to construct panel regression models to explore the differences in the influential factors of the PM2.5 concentration in three climate zones. The number of cities with PM2.5 concentration less than 35 µg/m3 increased in the different climate zones. The center of gravity of the PM2.5 concentration has remained at the junction of the temperate and subtropical monsoon climate zones. The PM2.5 concentration had a high positive spatial autocorrelation in the different climate zones. The high-high clustering areas were located in the south of the temperate monsoon climate zone and the north of the subtropical monsoon climate zone. There was an inverted "U-shaped" curve between the PM2.5 concentration and economic development in China that varied in different climate zones. Identifying the differences in the influential factors of PM2.5 concentration in different climate zones will help to accelerate the implementation of the EKC inflection point.

Differentiation Analysis on Carbon Emission Efficiency and Its Factors at Different Industrialization Stages: Evidence from Mainland China.

Industrial production is currently the main source of global carbon emissions. There are obvious differences in regional carbon emission efficiencies (CEE) at different industrial stages. We investigate CEE and explore its factors in mainland China at different industrialization stages from 2008-2020 using the super-SBM model with an undesirable output and the STIRPAT model. There is significant spatial heterogeneity in regional CEE, with gaps gradually widening. CEE's spatial heterogeneity in mid-industrialized provinces is narrowing, while in late-industrialized and post-industrialized provinces, it is widening. CEE's factors also differ in provinces at different industrialization stages. At the mid-industrialization stage, the industrial structure (IS) is the dominant factor, while population urbanization (PU) is dominant at the late-industrialization stage, and both PU and IS are dominant at the post-industrialization stage. Based on CEE's characteristics at different industrialization stages, we propose suggestions for green development.

miR-17-5p Promotes Glucose Uptake of HTR8/SVneo Trophoblast Cells by Inhibiting TXNIP/NLRP3 Inflammasome Pathway.

Introduction: Gestational diabetes mellitus (GDM) is one of the common metabolic disorders of pregnancy and results in poor pregnancy outcomes for both mother and fetus. MiR-17-5p is considered as the strongest predictor of metabolic syndrome status, but the relationship between GDM and miR-17-5p remains unclear. TXNIP, which leads to activation of NLRP3, is considered as a potential target of miR-17-5p, and the miR-17-5p/TXNIP/NLRP3 axis has been shown to play a major role in the occurrence and development of many metabolic diseases but has not been validated in GDM. Methods: MiR-17-5p was detected by RT-qPCR. The expression of TXNIP and NLRP3 in placenta was detected by immunofluorescence, RT-qPCR and Western blot. To explore the effect of miR-17-5p on TXNIP and NLRP3 and glucose uptake of HTR8/SVneo cells, miR-17-5p mimic and miR-17-5p inhibitor were transfected to achieve overexpression and inhibition. The interaction between miR-17-5p and TXNIP was confirmed by dual-luciferase reporter assay. Besides, glucose consumption of trophoblast cells was detected by glucose assay kit. Results: MiR-17-5p expression was down-regulated, while the expression of TXNIP and NLRP3 was up-regulated in GDM placental tissues. MiR-17-5p targeted TXNIP and inhibited its expression. MiR-17-5p also regulated NLRP3 expression and glucose uptake of HTR8/SVneo cells, which could be reversed by overexpression of TXNIP, suggesting that miR-17-5p improved glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis. The results were consistent with the above findings in high-glucose treated HTR8/SVneo cells. Conclusion: Our results suggested that miR-17-5p ameliorates the glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis, which may provide a new idea for offspring health of GDM patients.

Multidimensional effects of urbanization on PM2.5 concentration in China.

Recently, the contradiction between urbanization and the air environment has gradually attracted attention. However, most existing studies have explored the impact of single urbanization factors, such as population, the economy, or land, on PM2.5 and ignored the impact of multidimensional urbanization on PM2.5 concentration. Moreover, the heterogeneity in the mechanisms responsible for the PM2.5 concentration caused by multidimensional urbanization has not been thoroughly studied in different regions in China. Therefore, we investigate the spatial-temporal evolution characteristics of PM2.5 concentration in China during 1998-2019 by spatial analysis and dynamic panel models based on the environmental Kuznets curve (EKC). Then, we study the effects of multidimensional urbanization on PM2.5 concentration, and analyze the dominant factors in China's eight economic regions. During the study period, the PM2.5 concentration in China fluctuated before 2013 and gradually decreased thereafter. The PM2.5 concentration has significant regional differences in China. Spatially, the PM2.5 concentration is higher in the north than in the south and higher in the east than in the west. Additionally, there is a significant spatial spillover effect. Both population urbanization and economic urbanization show an inverted U-shaped relationship with PM2.5 concentration in China, which is consistent with the classical EKC theory. Due to other socioeconomic factors, the PM2.5 concentration tends to decrease linearly with increasing land urbanization rate. The effects of urbanization on the PM2.5 concentration in the eight economic regions in China show significant differences. The effect of land urbanization on the PM2.5 concentration is dominant in the Middle Yangtze River region, that of economic urbanization is dominant in northwestern China, and that of population urbanization is dominant in the remaining regions in China.

G-CSF: A vehicle for communication between trophoblasts and macrophages which may cause problems in recurrent spontaneous abortion.

INTRODUCTION: The etiology of approximately half of patients with recurrent spontaneous abortion (RSA) has yet to be established. Granulocyte-colony stimulating factor (G-CSF) exerts a protective effect on pregnancy and its absence may lead to pregnancy failure. However, the effects and mechanisms of G-CSF activities have not been fully explored. Therefore, we aimed at evaluating whether a loss of G-CSF induces RSA by affecting cell communication at the maternal-foetal interface. METHODS: Villous and decidual tissues were obtained from participants and expression levels of G-CSF determined by qRT-PCR, Western blot and immunohistochemistry. G-CSF levels in trophoblasts were downregulated by siRNA. Exosomes were extracted from trophoblasts and co-cultured with macrophages. Molecular expression levels of key genes were determined by qRT-PCR and Western blot. Migration and proliferation of cells were evaluated by transwell and CCK8 assays. The RSA mice models were intraperitoneally administered with G-CSF to assess pregnancy outcomes and expression profiles of G-CSF as well as its receptor at the mother-foetal interface. RESULTS: Relative to the decidua, G-CSF was highly expressed in the villus, and expression levels were low in RSA tissues compared to normal tissues. Down-regulation of G-CSF in the trophoblast cell line (HTR-8/SVneo) by siRNA was associated with a decrease in cell activities. Trophoblast-derived exosomes inhibited the activation of the macrophage cell line (RAW264.7), whereas G-CSF free exosomes had no effects on macrophage activation. Intraperitoneal administration of G-CSF improved pregnancy outcomes in RSA mice and increased the amounts of G-CSF at the maternal-foetal interface. DISCUSSION: G-CSF levels were downregulated in villi of RSA patients. The absence of G-CSF impaired the proliferation as well as migration capacities of trophoblasts, and weakened the suppression of trophoblasts against macrophages. This implies that suppressed G-CSF levels may be a key factor in RSA occurrence. G-CSF decreased the rate of abortion in RSA mice, thus, it could be a treatment option for RSA patients.

Synthesis and antioxidant activity of the inulin derivative bearing 1,2,3-triazole and diphenyl phosphate.

In this paper, the inulin derivative (3) bearing 1,2,3-triazole and diphenyl phosphate was successfully synthesized by CuAAC Click chemistry. Detailed structural characterization was determined using FTIR spectroscopy, 1H NMR spectroscopy, 13C NMR spectroscopy, and elemental analysis. The antioxidant activities against hydroxyl radicals, superoxide radicals, and DPPH radicals were estimated in vitro respectively. The results showed that the antioxidant activity of the inulin derivative (3) was significantly enhanced compared with inulin. The inulin derivative (3) exhibited stronger radical scavenging abilities, especially against hydroxyl radicals and superoxide radicals. The scavenging values of the inulin derivative (3) were 98.2% and 95.4% at 1.6 mg/mL against hydroxyl radicals and superoxide radicals respectively. Besides, the scavenging value of the inulin derivative (3) increased by about 40% to scavenge DPPH radicals at 1.6 mg/mL than inulin. The results showed that the inulin derivative (3) bearing 1,2,3-triazole and diphenyl phosphate exhibited tremendously enhanced antioxidant activity compared with inulin. The synthetic strategy might provide an effective way to prepare novel inulin antioxidant biomaterials.

Antifungal activity of double Schiff bases of chitosan derivatives bearing active halogeno-benzenes.

In this study, a series of chitosan derivatives bearing active halogenated aromatic imines were successfully synthesized via Schiff bases with the high degrees of substitution. Detailed structural characterization was carried out using Fourier transform infrared (FTIR) spectroscopy, solid-state 13C nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis. Besides, the antifungal activity against three common plant pathogenic fungi, including Botrytis cinerea, Fusarium oxysporum f. sp. cucumerinum, and Fusarium oxysporum f. sp. niveum, was investigated using in vitro hyphal measurements. The results showed that double Schiff bases of chitosan derivatives exhibited enhanced antifungal activity compared with chitosan, especially at 1.0 mg/mL. The double Schiff bases of chitosan bearing halogeno-benzenes showed >95% inhibitory indices at 1.0 mg/mL against Botrytis cinereal since halogens had the stronger electron-withdrawing property. The higher degree of substitution was another positive effect to improve the antifungal activity. This study provides a practical strategy to synthesize new double Schiff bases of chitosan derivatives bearing halogeno-benzenes, which could be developed into stronger antifungal agents.

Upregulation of IL-15 in the placenta alters trophoblasts behavior contributing to gestational diabetes mellitus.

BACKGROUND: Interleukin-15 (IL-15), a member of the 'four α-helix bundle' cytokine family, has been associated with many inflammatory and metabolic diseases. Abnormal expression of IL-15 has been linked to the occurrence and development of obesity and diabetes. However, there is a paucity of research on the involvement of IL-15 in Gestational Diabetes Mellitus (GDM). This study aims at investigating the role of IL-15 in the pathogenesis of GDM. RESULTS: IL-15 was consistently expressed in the placenta throughout pregnancy and dynamically changed with pregnancy progress. Trophoblasts have been identified as the major source of IL-15 in the placenta. Expression of IL-15 was significantly increased in the placenta of GDM and in the trophoblasts cultured with high glucose (HG). In our study, expression of IL-15 in the placenta was positively correlated with blood glucose concentration of 75 g Oral Glucose Tolerance Test (OGTT), and was inversely correlated with weight of newborns. Further investigations in vitro showed that exogenous addition of IL-15 promoted trophoblasts proliferation, improved invasion and tube formation ability by activating the JAK/STAT signaling pathway, which be blocked by JAK inhibitors. CONCLUSION: Our results demonstrated that IL-15 expression in the placenta was dynamically changing during pregnancy, and it was upregulated in the placenta of GDM patients. Furthermore, IL-15 altered the biological behavior of trophoblasts through JAK/STAT signaling pathway in vitro, and may contributed to the placental pathology of GDM. Our findings provide a new direction for studying the pathophysiological changes of placenta in GDM.