Fish oil supplementation and risk of incident systemic lupus erythematosus: a large population-based prospective study.

BACKGROUND: Although fish oil has been considered to have an anti-inflammatory effect and has been proven to play a beneficial role in the incidence of numerous diseases, the association between fish oil supplementation and the risk of systemic lupus erythematosus (SLE) is still unknown. This study aimed at evaluating the correlation between fish oil use and incident SLE in a large population-based prospective cohort. METHODS: 390,277 participants without SLE at baseline from the UK Biobank were enrolled. Fish oil use was ascertained through a touchscreen questionnaire at baseline. The incidence of SLE was identified by the International Classification of Diseases version 10 code in medical records or self-report. Cox proportional hazard models were employed to estimate the association between fish oil use and SLE risk. RESULTS: Fish oil users accounted for 31.47% of participants. During a median follow-up duration of 11.57 years, 141 participants without fish oil use (4.56/100 000 person-years) and 68 participants with fish oil use (4.78/100 000 person-years) developed SLE. In four models with adjustments for different amounts of confounders, there was no significant difference in the risk of SLE between fish oil users and fish oil non-users (all p-values > 0.05). In subgroup analyses, we found that fish oil supplementation was associated with a lower risk of SLE among females with ultraviolet radiation ≥ 3 h/day (hazard ratio: 0.63, 95% confidence interval: 0.40-0.98), which turned insignificant after further adjustment for female-related factors and sun protection measures. CONCLUSIONS: No significant association between fish oil use and overall incident SLE was observed, except in females exposed to prolonged ultraviolet radiation. Subgroup analysis suggested that females exposed to prolonged ultraviolet radiation might benefit from fish oil supplementation in terms of preventing SLE, but it needs to be confirmed in further studies.

The PP2A inhibitor LB-100 mitigates lupus nephritis by suppressing tertiary lymphoid structure formation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and autoantibody production. Patients with SLE face a substantial risk of developing lupus nephritis (LN), which imposes a substantial burden on both patients and their families. Protein phosphatase 2A (PP2A) is a widely distributed serine/threonine phosphatase that participates in regulating multiple signaling pathways. Inhibition of PP2A has been implicated in the treatment of various diseases. LB-100, a small molecule inhibitor of PP2A, has demonstrated anti-tumor therapeutic effects and high safety profile in preclinical experiments. However, the role of PP2A and its inhibitor has been insufficiently studied in LN. In this study, we assessed the potential effects of LB-100 in both MRL/lpr mice and R848-induced BALB/c mice. Our findings indicated that LB-100 administration led to reduced spleen enlargement, decreased deposition of immune complexes, ameliorated renal damage, and improved kidney function in both spontaneous and R848-induced lupus mouse models. Importantly, we observed the formation of tertiary lymphoid structures (TLSs) in the kidneys of two distinct lupus mouse models. The levels of signature genes of TLS were elevated in the kidneys of lupus mice, whereas LB-100 mitigated chemokine production and inhibited TLS formation. In addition, we confirmed that inhibition or knockdown of PP2A reduced the production of T cell-related chemokines by renal tubular epithelial cells (RTEC). In summary, our study highlighted the renal protective potential of the PP2A inhibitor LB-100 in two distinct lupus mouse models, suggesting its potential as a novel strategy for treating LN and other autoimmune diseases.

Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage-myofibroblast transition.

Iguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of action, iguratimod has been observed to have antifibrotic effects in the lung and skin; however, its effect on renal fibrosis remains unknown. This study aimed to investigate whether iguratimod could affect renal fibrosis progression. Three different concentrations of iguratimod (30 mg/kg/day, 10 mg/kg/day, and 3 mg/kg/day) were used to intervene in unilateral ureteral obstruction (UUO) model mice. Iguratimod at 10 mg/kg/day was observed to be effective in slowing UUO-mediated renal fibrosis. In addition, stimulating bone marrow-derived macrophages with IL-4 and/or iguratimod, or with TGF-ß and iguratimod or SRC inhibitors in vitro, suggested that iguratimod mitigates the progression of renal fibrosis in UUO mice, at least in part, by inhibiting the IL-4/STAT6 signaling pathway to attenuate renal M2 macrophage infiltration, as well as by impeding SRC activation to reduce macrophage-myofibroblast transition. These findings reveal the potential of iguratimod as a treatment for renal disease.

Changing respiratory pathogens infection patterns after COVID-19 pandemic in Shanghai, China.

To assess the positive rate of 11 respiratory pathogens in 2023, providing a comprehensive summary and analysis of the respiratory infection patterns after COVID-19 pandemic. The study comprised 7544 inpatients suspected of respiratory infections who underwent respiratory pathogen multiplex polymerase chain reaction tests from July 2022 to December 31, 2023. We analyzed the positive rate of 11 pathogens over 18 months and the characterization of infection patterns among different age groups and immune states. Among 7544 patients (age range 4 months to 104 years, 44.99% female), the incidence of infected by at least one of the 11 pathogens was 26.07%. Children (55.18%, p < 0.05) experienced a significantly higher infection probability than adults (20.88%) and old (20.66%). Influenza A virus (8.63%), Mycoplasma pneumoniae (5.47%), and human rhinovirus (5.12%) were the most common pathogens. In children, M. pneumoniae (35.96%) replaced the predominant role of human respiratory syncytial virus (HRSV) (5.91%) in the pathogen spectrum. Age, immunosuppressed state, and respiratory chronic conditions were associated with a significantly higher risk of mixed infection. Immunosuppressed patients were more vulnerable to human coronavirus (4.64% vs. 1.65%, p < 0.05), human parainfluenza virus (3.46% vs. 1.69%, p < 0.05), and HRSV (2.27% vs. 0.55%, p < 0.05). Patterns in respiratory infections changed following regional epidemic control measures and the COVID-19 pandemic.

Gastrodinol derivatives and prenylated flavones from the flower branch of Gastrodia elata.

Based on the research progress and traditional usage with whole herbal of the TCM "Tianma", chemical studies herein on the flower branch of Gastrodia elata were carried out in-depth and got 13 compounds including the gastrodinols (1-4), the flavonoid morins (5-8, 11-12), together with the specialist mulberrofurans (9, 13) and gastrodiamide (10) for the first time from the species. The antibacterial and cholinesterase inhibitory activities were then evaluated and the results showed that compounds 5, 11, 12, 13 have good activity against anti-methicillin-resistant Staphylococcus aureus, and compounds 9, 13 had good acetylcholinesterase inhibitory activity. All these results provide new chemical composition for better understanding the traditional application of "Tianma" and for exploring new pharmacological ingredients.

Saa3 promotes pro-inflammatory macrophage differentiation and contributes to sepsis-induced AKI.

Sepsis-induced acute kidney injury (SAKI) is a life-threatening condition with complex pathophysiology, often exacerbated by immune cell dysregulation. In this comprehensive study, we leverage publicly available single-cell RNA sequencing (scRNA-seq) datasets to unravel the intricate immune responses occurring during SAKI, shedding light on macrophages as critical players. Specifically, we identify Saa3, a gene primarily expressed in macrophages, as a potent pro-inflammatory cytokine in SAKI. Saa3hi Ccl2hi monocyte-derived infiltrated macrophages (IMs) emerge as a central effector subset, fostering inflammation, and directly engaging with renal cells. Our findings suggest that Saa3 may be a promising predictive marker of SAKI, although further exploration of human homologs is warranted.

The Relationship Between Heavy Metals and Missed Abortion: Using Mediation of Serum Hormones.

Accumulating evidence suggests that heavy metal exposure may have adverse effects on the fetal development. Furthermore, disruption of serum hormone homeostasis can result in the adverse pregnancy outcomes. Therefore, this study aimed to investigate the potential association between heavy metals and missed abortion, with a focus on whether serum hormones mediate this relationship. The concentrations of heavy metals and hormones in serum were measured in this case-control study. Statistical models including, logistic regression model, principal component analysis (PCA), and weighted quantile sum (WQS) regression model were employed to examine the relationship between heavy metals, serum hormones, and missed abortion. Furthermore, the mediation analysis was performed to assess the role of serum hormones as potential mediators in this relationship. This study revealed significant associations between heavy metal exposure and missed abortion. Notable, the WQS index weight, which was mainly influenced by copper (Cu) and zine (Zn), is associated with missed abortion. Moreover, heavy metals including manganese (Mn), nickel (Ni), Zn, arsenic (As), Cu, cadmium (Cd), and lead (Pb) were found to be associated with serum levels of ß-human chorionic gonadotropin (ß-hCG), progesterone (P), estradiol (E2), and lactogen (HPL). In addition, the mediation analysis indicated that ß-hCG explained a portion of the association (ranging from 18.77 to 43.51%) of between Mn, Ni, Zn, and As exposure and missed abortion. Serum P levels explained 17.93 to 51.70% of the association between Ni, Cu, and As exposure and missed abortion. Serum E2 levels played a significant mediating role, explaining a portion of the association (ranging from 22.14 to 73.60%) between Mn, Ni, Cu, As, Cd, and Pb exposure and missed abortion. Our results suggested that ß-hCG, P, and E2 are one of the potential mediators in the complex relationship between heavy metals exposure and missed abortion. These results highlight the importance of considering both heavy metal exposure and serum hormone levels in understanding the etiology of missed abortion.

Nlrp3 Deficiency Alleviates Lipopolysaccharide-Induced Acute Kidney Injury via Suppressing Renal Inflammation and Ferroptosis in Mice.

The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a vital component of many inflammatory responses. Here, we intended to investigate the involvement of NLRP3 in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (S-AKI) and explore its mechanisms. For the first time, we validated elevated NLRP3 expression in the renal tissues of S-AKI patients by immunohistochemistry analysis. Through LPS injection in both wild-type and Nlrp3-/- mice, a S-AKI model was developed. It was found that LPS-induced kidney injury, including an abnormal morphology in a histological examination, abnormal renal function in a laboratory examination, and an increase in the expression of AKI biomarkers, was dramatically reversed in Nlrp3-deficient mice. Nlrp3 deletion alleviated renal inflammation, as evidenced by the suppression of the expression of pro-inflammatory cytokines and chemokines. A combinative analysis of RNA sequencing and the FerrDb V2 database showed that Nlrp3 knockout regulated multiple metabolism pathways and ferroptosis in LPS-induced S-AKI. Further qPCR coupled with Prussian blue staining demonstrated that Nlrp3 knockout inhibited murine renal ferroptosis, indicating a novel mechanism involving S-AKI pathogenesis by NLRP3. Altogether, the aforementioned findings suggest that Nlrp3 deficiency alleviates LPS-induced S-AKI by reducing renal inflammation and ferroptosis. Our data highlight that NLRP3 is a potential therapeutic target for S-AKI.

Multi-omics analysis of DNA replication-associated primase polymerase (PRIMPOL) in pan-cancer: a potential target for prognosis and immune response.

BACKGROUND: It is critical to understand the mechanisms of human cancers in order to develop the effective anti-cancer therapeutic strategies. Recent studies indicated that primase polymerase (PRIMPOL) is strongly associated with the development of human cancers. Nevertheless, a systematic pan-cancer analysis of PRIMPOL remains to be further clarified. METHOD: Comprehensive multi-omics bioinformatics algorithms, such as TIMER2.0, GEPIA2.0 and cBioPortal, were utilized to evaluate the biological roles of PRIMPOL in pan-cancer, including the expression profiles, genomic alterations, prognostic values and immune regulation. RESULTS: PRIMPOL was upregulated in glioblastoma multiforme and kidney renal clear cell carcinoma. The brain lower grade glioma patients with enhanced PRIMPOL expression displayed poor prognostic values. We also demonstrated the PRIMPOL's immunomodulating effects on pan-cancer as well as its genomic changes and methylation levels. The aberrant expression of PRIMPOL was linked to various cancer-associated pathways, including DNA damage response, DNA repair, and angiogenesis, according to single-cell sequencing and function enrichment. CONCLUSIONS: This pan-cancer analysis offers a thorough review of the functional roles of PRIMPOL in human cancers, suggesting PRIMPOL as a potentially important biomarker for the progression and immunotherapy of various cancers.

Health risk assessment of lead via the ingestion pathway for preschool children in a typical heavy metal polluted area.

The problems of environmental lead (Pb) pollution caused by mining activities have attracted global attention. Preschool children are vulnerable to exposure to Pb from the environment. To investigate the health risk of multiple exposures to Pb via oral ingestion (soil, water, rice, wheat, and vegetables) for preschool children in typical polluted areas, in this study, preschool children in Baiyin city were selected as the potential receptors, Pb concentrations in 28 soil samples and 33 vegetable samples were collected and measured. In addition, the Pb concentrations in local water, rice, and wheat were obtained by searching the literature. The Monte Carlo simulation was used in the uncertainty and sensitivity analysis of the parameters. Results showed that Pb concentrations in spinach, tomato, cushaw, lettuce, broad bean, pea, eggplant, and radish exceeded the standards (GB 2762-2017), and 42.86% of soil samples exceeded screening values (GB 15618-2018). The non-carcinogenic risk was as high as 3.58. Vegetables and wheat were the major contributors in the oral ingestion pathway. Furthermore, the carcinogenic risk of preschool children was 6.02E-06, which was acceptable. Monte Carlo simulations showed that health risk assessment results were most likely to be influenced by Pb concentrations in the media. In conclusion, the food safety of vegetables in soil-polluted areas deserves more attention, and certain measures should be taken to reduce the health risks to preschool children.

Assessment of heavy metal pollution and preschool children health risk in urban street dusts from different functional areas in a typical industrial and mining city, NW China.

To assess the pollution characteristics and health risks associated with street dust exposure among preschool children in typical industrial and mining areas, we analyzed heavy metal concentrations of 20 urban street dusts in commercial area (CA), residential area (RA), scientific and educational area (SEA) and industrial and mining area (IMA) from Baiyin, NW China. The average concentrations of Cr, Mn, Ni, Cu, Zn, Cd, Pb, As and Hg were 614.96, 484.25, 1757.74, 6868.86, 893.19, 77.62, 1473.99, 15.01 and 0.59 mg·kg-1, respectively. The ecological risk indexes for Cd, Cu and Hg were found as 20,075.20, 1425.07 and 1174.86, respectively, and the ecological risk was extremely high. The pollution load indexes (PLI) were > 1 for all four functional areas. The total hazard index (THI) for different functional areas were more than 1, and the main exposure pathway for children was ingestion route. Heavy metals in street dust of the IMA had the highest THI for children (43.88), and HI of Pb was being most significant (17.38). In addition, the carcinogenic risk to children via the respiratory route was acceptable. Furthermore, factor analysis and cluster analysis classified heavy metals into two groups, indicating common anthropogenic sources for Cr, Ni, Cu, Zn, Cd, Pb, As and Hg. In conclusion, urban street dusts from industrial and mining area of Baiyin, NW China were found polluted by heavy metals and the pollution would pose an obvious non-carcinogenic risk to preschool children.

The polar and nonpolar interfaces influenced of magnetism in LaMnO3-based superlattices.

The interface of perovskite heterostructures has been shown to exhibit various electronic and magnetic phases such as two-dimensional electron gas, magnetism, superconductivity, and electronic phase separation. These rich phases are expected due to the strong interplay between spin, charge, and orbital degree of freedom at the interface. In this work, the polar and nonpolar interfaces are designed in LaMnO3-based (LMO) superlattices to investigate the difference in magnetic and transport properties. For the polar interface in a LMO/SrMnO3 superlattice, a novel robust ferromagnetism, exchange bias effect, vertical magnetization shift, and metallic behaviors coexist due to the polar catastrophe, which results in a double exchange coupling effect in the interface. For the nonpolar interface in a LMO/LaNiO3 superlattice, only the ferromagnetism and exchange bias effect characteristics exist due to the polar continuous interface. This is attributed to the charge transfer between Mn3+ and Ni3+ ions at the interface. Therefore, transition metal oxides exhibit various novel physical properties due to the strong correlation of d electrons and the polar and nonpolar interfaces. Our observations may provide an approach to further tune the properties using the selected polar and nonpolar oxide interfaces.

The Effect of Different Moderate Thermal Modification Durations on the Wood Properties of American Alder.

To investigate the effect of moderate thermal modification (TM) on wood properties, American alder (Alnus rubra) wood was treated at 140 °C for 4 h, 8 h and 13 h, the physical and mechanical properties, dimensional stability and color changes of wood were compared and studied. The results showed that the absolute dry density of moderate-TM wood decreased significantly with time except for the 4 h treatment. Moderate TM can significantly reduce the residual stress of wood up to 90.3%. There were no significant differences in MOR and MOE between most moderate TM wood and the control group; moderate TM decreased the moisture absorption and water up-taking of wood significantly; compared to the control group, the swelling of TM wood for 13 h decreased by 24.2% and 16.0% in the tangential and radial direction, respectively, showing a significant improvement in dimensional stability. There were almost no color changes even when wood endured 140 °C and 13 h TM. The moderate TM at 140 °C for 13 h can efficiently improve wood dimensional stability and retains the natural color of wood while causing almost no damage to the wood's mechanical strength.

Effect of Samples Size on the Water Removal and Shrinkage of Eucalyptus urophylla × E. grandis Wood during Supercritical CO2 Dewatering

Eucalyptus urophydis E. grandis green wood with different lengths were dewatered using CO2 that was cyclically alternated between the supercritical fluid and gas phases. The results indicate that shorter specimens can be dewatered to below the fiber saturation point (FSP). There was no significant difference in the dewatering rate between the specimens of 20 and 50 mm in length. The dewatering was faster when the moisture content (MC) was over the FSP, leading to a greater gradient and a non-uniform distribution of moisture. The MC distributions in all specimens had no clear differences between in tangential and radial directions. Supercritical CO2 dewatering generated a different moisture gradient than conventional kiln drying. Most water was dewatered from the end-grain section of the wood along the fiber direction, but a small amount of water was also removed in the transverse directions. There was no deformation in the specimens when the MC was above the FSP.

Identification of Downregulated Exosome-Associated Gene ENPP1 as a Novel Lipid Metabolism and Immune-Associated Biomarker for Hepatocellular Carcinoma.

Exosome plays an important role in the occurrence and development of tumors, such as hepatocellular carcinoma (LIHC). However, the functions and mechanisms of exosome-associated molecules in LIHC are still underexplored. Here, we investigated the role of the exosome-related gene ENPP1 in LIHC. Comprehensive bioinformatics from multiple databases revealed that ENPP1 was significantly downregulated in LIHC tissues. The patients with downregulated ENPP1 displayed a poor prognosis. Immunohistochemistry (IHC) was used to further confirm the downregulated ENPP1 in LIHC tissues. In addition, the coexpression network of ENPP1 was also explored to understand its roles in the underlying signaling pathways, including fatty acid degradation and the PPAR signaling pathway. Simultaneously, GSEA analysis indicated the potential roles of ENPP1 in the lipid metabolism-associated signaling pathways in the pathogenesis of LIHC, including fatty acid metabolism, fatty acid synthesis, and so on. Finally, immunological analysis indicated that ENPP1 might also be involved in multiple immune-related features, including immunoinhibitors, immunostimulators, and chemokines. Taken together, these findings could enhance our understanding of ENPP1 in LIHC pathogenesis and immune response and provide a new target for ENPP1-related immunotherapy in clinical treatment.

Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors.

The primary or acquired resistance to anti-VEGF inhibitors remains a common problem in cancer treatment. Therefore, identifying potential biomarkers enables a better understanding of the precise mechanism. Through the GEO database, three profiles associated with bevacizumab (BV) resistance to ovarian cancer, glioma, and non-small-cell lung carcinoma, respectively, were collected for the screening process, and two genes were found. A-kinase anchor protein 12 (AKAP12), one of these two genes, correlates with tumorigenesis of some cancers. However, the role of AKAP12 in pan-cancer remains poorly defined. The present study first systematically analyzed the association of AKAP12 with anti-VEGF inhibitors' sensitivity, clinical prognosis, DNA methylation, protein phosphorylation, and immune cell infiltration across various cancers via bioinformatic tools. We found that AKAP12 was upregulated in anti-VEGF therapy-resistant cancers, including ovarian cancer (OV), glioblastoma (GBM), lung cancer, and colorectal cancer (CRC). A high AKAP12 expression revealed dismal prognoses in OV, GBM, and CRC patients receiving anti-VEGF inhibitors. Moreover, AKAP12 expression was negatively correlated with cancer sensitivity towards anti-VEGF therapy. Clinical prognosis analysis showed that AKAP12 expression predicted worse prognoses of various cancer types encompassing colon adenocarcinoma (COAD), OV, GBM, and lung squamous cell carcinoma (LUSC). Gene mutation status may be a critical cause for the involvement of AKAP12 in resistance. Furthermore, lower expression of AKAP12 was detected in nearly all cancer types, and hypermethylation may explain its decreased expression. A decreased phosphorylation of T1760 was observed in breast cancer, clear-cell renal cell carcinoma, and lung adenocarcinoma. For the immunologic significance, AKAP12 was positively related to the abundance of pro-tumor cancer-associated fibroblasts (CAFs) in various types of cancer. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that "cell junction organization" and "MAPK pathway" participated in the effect of AKAP12. Importantly, we discovered that AKAP12 expression was greatly associated with metastasis of lung adenocarcinoma as well as differential and angiogenesis of retinoblastoma through investigating the single-cell sequencing data. Our study showed that the dual role of AKAP12 in various cancers and AKAP12 could serve as a biomarker of anti-VEGF resistance in OV, GBM, LUSC, and COAD.

A Prognostic Signature Consisting of Pyroptosis-Related Genes and SCAF11 for Predicting Immune Response in Breast Cancer.

Pyroptosis, characterized as an inflammasome-mediated cell death pathway, may be participated in tumorigenesis and progression. However, the underlying molecular function and mechanism of pyroptosis in BRCA remain unclear. In our study, we aimed to develop a prognostic signature in BRCA based on pyroptosis-associated genes. Data was downloaded from TCGA database, and then we screened 760 female BRCA samples and 104 normal breast tissues as the training set. Seven pyroptosis-related genes (CASP9, GPX4, IL18, NLRC4, SCAF11, TIRAP, and TNF) were identified as the pyroptosis-related prognostic model for BRCA using LASSO Cox regression. We subsequently tested the prognostic value of pyroptosis-associated gene signature in a validation set, GSE 20685. Time-dependent receiver operating characteristic analysis demonstrated the credible predictive capacity of this pyroptosis-associated gene signature. The area under the curves were 0.806 at 3 years, 0.787 at 5 years, 0.775 at 8 years, and 0.793 at 10 years in the training set, and 0.824 at 5 years, 0.808 at 8 years, and 0.790 at 10 years in the validation set. Furthermore, there are currently few data on SCAF11 regulating pyroptosis. To clarify this issue, we performed integrative bioinformatics and experimental analysis. Knocking down SCAF11 possessed an anti-cancer effect in terms of inhibiting cell viability and suppressing colony-formation in in-vitro functional assays. Meanwhile, the biological functions of SCAF11 in BRCA were further validated with several algorithms, such as Xiantao tool, LinkedOmics, GEPIA2, and TISIDB. These findings indicated that the expression of SCAF11 was significantly correlated with diverse tumor-infiltrating lymphocytes (TILs), including T central memory cell (Tcm), and type 2 T helper cell (Th2), etc. Functional enrichment analysis suggested that co-expression genes of SCAF11 primarily participated in inflammation and immune-related signaling pathways, such as oxidative phosphorylation, antimicrobial humoral response, and immunoglobulin complex. Moreover, SCAF11 expression was positively correlated with several immune checkpoints, including PD-L1, B7H3, and PDCD1LG2. Taken together, this study uncovered that pyroptosis-associated gene signature might be applied as an effective independent predictor in patients with BRCA. The pyroptosis-related gene SCAF11 might play potential roles in the regulation of immune microenvironment in BRCA.

In missed abortion the decrease of IGF-1 down-regulates PI3K/AKT signaling pathway reducing the secretion of progesterone and ß-hCG.

OBJECTIVE: To explore whether the reduction of IGF-1 in missed abortion down-regulates PI3K/AKT signaling pathway, thereby causing trophoblast cell apoptosis and reducing the secretion of ß-hCG and progesterone. DESIGN: 12 pairs of serum and villous tissues were selected from missed abortion patients and normal early pregnant women who had terminated pregnancy by artificial abortion. The subjects in two groups had same age and gestational week. Wes Simple Western system and qRT-PCR were used to detect the expression of IGF-1, IGF-1R, PI3K/AKT signaling pathway and apoptosis-related factors in villous tissues. Radioimmunoassay and Enzyme-linked immunosorbent assay were used to detect ß-hCG, progesterone and IGF-1 in serum. RESULTS: The serum levels of ß-hCG, progesterone and IGF-1 were decreased in missed abortion group than those in normal early pregnant women. In addition, compared with normal early pregnant women, the genes and proteins levels of IGF-1 and PI3K/AKT signaling pathway and anti-apoptosis related factors were significantly decreased. CONCLUSIONS: Our results suggested that the reduction of IGF-1 in missed abortion patients could down-regulate the expression of PI3K/AKT signaling pathway, thereby increasing the apoptosis of trophoblast cells, leading to decreased secretion of ß-hCG and progesterone, which may be one of the important mechanisms of missed abortion.

Potential Biological Roles of Exosomal Long Non-Coding RNAs in Gastrointestinal Cancer.

Exosomes, a type of extracellular vesicles (EVs), are secreted by almost all cells and contain many cellular constituents, such as nucleic acids, lipids, and metabolites. In addition, they play a crucial role in intercellular communication and have been proved to be involved in the development and treatment of gastrointestinal cancer. It has been confirmed that long non-coding RNAs (lncRNAs) exert a range of biological functions, such as cell metastasis, tumorigenesis, and therapeutic responses. This review mainly focused on the emerging roles and underlying molecular mechanisms of exosome-derived lncRNAs in gastrointestinal cancer in recent years. The biological roles of exosomal lncRNAs in the pathogenesis and therapeutic responses of gastrointestinal cancers were also investigated.

Associations of maternal blood mercury with preeclampsia and birth outcomes.

BACKGROUND: Mercury (Hg) is a highly toxic substance, and its harmful effects on maternal and infant health have been reported. Yet, the associations of Hg exposure with preeclampsia (PE) and adverse birth outcomes are not well understood. OBJECTIVE: The aim of this study was to investigate the potential effects of maternal Hg exposure on PE and birth outcomes. METHODS: We conducted a case-control study with 84 participants in China. Logistic models were used to estimate odds ratios for PE risk and birth outcomes according to maternal blood Hg levels, adjusting for potential confounding factors. RESULTS: Elevated blood Hg levels were associated with increased risks of mild PE (aOR, 7.03; 95% CI, 1.61, 30.62; P < 0.01) and severe PE (aOR, 47.55; 95% CI, 5.27, 429.05; P < 0.05). We also found that increased blood Hg levels were associated with low birth weight (aOR, 1.12; 95% CI, 1.00, 1.25; P < 0.05) and preterm birth (PTB) (aOR, 1.22; 95% CI, 1.08, 1.38; P < 0.05). CONCLUSIONS: Our study provided evidence that elevated blood Hg levels were significantly associated with an increased risk of PE. In addition, our findings support that increased blood Hg levels might be associated with low birth weight and PTB.