Roles of RNA m5C modification patterns in prognosis and tumor microenvironment infiltration of diffuse large B-cell lymphoma.

Genetic and epigenetic aberrations display an essential role in the initiation and progression of diffuse large B-cell lymphoma (DLBCL). 5-methylcytosine (m5C), a common RNA modification, regulates various cellular processes and contributes to tumorigenesis and cancer progression. However, m5C alterations in DLBCL remain unclear. Our research constructed an m5C prognostic model utilizing GEO data sets, which can efficiently predict the prognosis of patients with DLBCL, and verified the m5C prognostic model genes by immunohistochemistry analysis. This model was constructed using unsupervised consensus clustering analyses, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses. Based on the expression of m5C genes in the model, patients with DLBCL could be effectively divided into groups with significant survival time differences. The m5C risk-score signature demonstrated a highly significant independent prognostic value. Results from tumor microenvironment analyses revealed that m5C genes altered the infiltration of eosinophils, Tregs, and M2 macrophages. Additionally, they regulated T cell activation by modulating the expression of CTLA4, PDL1, B2M, CD8A, ICOS, and other relevant immune checkpoint expressions. In conclusion, our study presents a robust m5C prognostic model that effectively predicts prognosis in DLBCL. This model may offer a new approach for prognostic stratification and potential therapeutic interventions for patients with DLBCL.

A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients.

BACKGROUND: Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. OBJECTIVES: To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. MATERIALS AND METHODS: 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity. RESULTS: Six circular RNAs including hsa_circ_0058058, hsa_circ_0008045, hsa_circ_0084789, hsa_circ_0000550, hsa_circ_0007422, and hsa_circ_0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score = 1.094×hsa_circ_0058058+0.697×hsa_circ_0008045+0.718×hsa_circ_0084789-0.591×hsa_circ_0000550-0.435×hsa_circ_0007422-1.017×hsa_circ_0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval. DISCUSSION AND CONCLUSION: Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs.

The association of serum toxic metals and essential elements during early pregnancy with body mass index trajectory of infants during the first years: A prospective study.

To the best of our knowledge, prior research has yet to delve into the combined and interactive relationships between maternal exposure to essential elements and toxic metals and infancy's continuous growth and trajectories. This study aims to discern infant growth trajectories in the first year of life and to determine the associations of maternal serum levels of essential elements and toxic metals with growth trajectory. Within a Chinese prospective cohort in 2019 - 2021, 407 mother-infant pairs were included, and the serum levels of five essential elements (zinc, calcium, copper, magnesium and iron) and two toxic metals (cadmium and lead) in early pregnancy were assessed. The growth trajectory of infants was followed until age one year. Raw BMI and height values were transformed to age- and sex-specific BMI and height standard deviation (SD) scores. Latent-class group-based trajectory models and piecewise linear mixed regression were estimated to determine infant growth trajectories and growth velocity, respectively. The individual relationship between maternal metallic element levels and infant growth trajectory was examined using multinomial logistic regression models and linear mixed regression, while joint associations and interactive relationships were explored using Bayesian kernel machine regression (BKMR) following confounder adjustments. Four distinct trajectory patterns based on BMI-z score (low-rapid BMI gain group, normal-stable BMI group, very low-rapid BMI gain group and normal-rapid BMI gain group) and length-for-age (high-stable length group, low-stable length group, normal-rapid length gain group, very low-rapid length gain group) were identified during the first year post-birth, respectively. In single-metal and multiple-metal models, infants born to mothers with higher serum Zn and lower serum Cu levels were associated with a normal-rapid BMI gain trajectory during the first year. Serum Cu exhibited a positive correlation with the rate of BMI change solely in infants aged 6-12 months. Further, the BKMR analysis revealed a statistically significant and negative joint effect of the five essential elements on the likelihood of normal-rapid BMI/length gain trajectory when serum levels of these elements fell below the 70th percentile compared to median levels. In addition, high levels of serum copper and calcium interactively affect the rates of BMI change during 6-12 months old (ß: -0.21, 95% CI: -0.44, -0.03, P = 0.04, P-interaction=0.04). In conclusion, maternal trace elements at early pregnancy are linked to infant growth patterns and growth velocity in the first year of life.

Serum aspartate aminotransferase, a novel potential biomarker of prognosis in extranodal natural killer/T cell lymphoma, nasal type.

BACKGROUND: Aspartate aminotransferase (AST), an indicator of liver cell damage, was related to the prognosis of certain malignant tumors. OBJECTIVE: This study examined the predictive value of AST in patients with extranodal natural killer/T cell lymphoma (ENKTL). METHODS: We reviewed 183 cases diagnosed with ENKTL and selected 26 U/L as the optimum cut-off value of AST. We used the univariate and multivariate Cox regression to compare the different AST groups' overall survival (OS) and progression-free survival (PFS). RESULTS: Prior to propensity score matching (PSM), Kaplan-Meier analysis showed that patients in the low AST subgroup had better OS and PFS than the high AST subgroup. Multivariate analysis revealed that AST was an independent indicator for prognosis. After PSM, the low AST subgroup maintained a significantly better OS and PFS than the high AST subgroup. CONCLUSION: AST might represent a significant prognostic marker for ENKTL patients.

Combined exposure to multiple essential elements and cadmium at early pregnancy on gestational diabetes mellitus: a prospective cohort study.

Background: Minerals and trace elements were involved in the pathogenesis and progression of diabetes. However, the association of mixed exposure to essential elements and toxic elements with gestational diabetes mellitus (GDM) is poorly understood. Objective: This study aims to examine the associations between serum calcium (Ca), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and cadmium (Cd) concentrations in early pregnancy and GDM risk in Chinese pregnant women. Method: A total of 1,168 pregnant women were included in this prospective cohort study. The concentrations of serum elements were measured using the polarography method before 14 gestational weeks and an oral glucose tolerance test was conducted at 24-28 gestational weeks to diagnose GDM. Binary logistic regression analysis and restricted cubic spline were applied to evaluate the association between serum individual element and GDM. Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were used to assess the associations between mixed essential elements and Cd exposure and GDM risk. Results: The mean concentrations of Zn (124.65 vs. 120.12 µmol/L), Fe (135.26 vs. 132.21 µmol/L) and Cu (23.33 vs. 23.03 µmol/L) in the GDM group were significantly higher than those in the control group. Single-element modeling results suggested that second and fourth-quartile maternal Zn and Fe concentration, third and fourth-quartile Cu concentration and fourth-quartile Ca concentration were associated with an increased risk of GDM compared to first-quartile values. Restricted cubic spline analysis showed U-shaped and non-linear relationships between Cd and GDM. According to the BKMR models and WQS analyses, a six-element mixture was significantly and positively associated with the risk of GDM. Additionally, Cd, Zn, and Cu contributed the most strongly to the association. Conclusion: Serum Zn, Cu, Fe, and Ca exposure during early pregnancy showed a positive association with GDM in the individual evaluation. The multiple-evaluation showed that high levels of elements mixture, particularly Cd, Zn, and Cu, may promote the development of GDM.

GRPR down-regulation inhibits spermatogenesis through Ca2+ mediated by PLCß/IP3R signaling pathway in long-term formaldehyde-exposed rats.

Formaldehyde (FA), which is known as an air pollutant, has been proven to induce male infertility. However, the underlying mechanism of FA-induced male infertility remains elusive. In this study, 24 male SD rats were exposed to different levels of FA (0, 0.5, 2.46, and 5 mg/m3) for eight consecutive weeks. Through HE staining and sperm smear, we observed that FA exposure resulted in spermatogenic injury and the sperm quality decreased in rats. The qRT-PCR and Western blot analysis further revealed that GRPR was down-regulated in testicular tissues of FA-exposed rats as well as primary spermatogenic cells. Meanwhile, ZDOCK uncovered an interaction between GRPR and PLCß. In addition, the CCK8, Fluo 3-AM and Flow cytometry results showed that FA exposure suppressed the expression of GRPR, PLCß and IP3R, consequently reducing the Ca2+ concentration in spermatogenic cells, inducing apoptosis and inhibiting proliferation of spermatogenic cells. Moreover, rescue experiments confirmed that promoting GRPR could improve intracellular Ca2+ concentration by upregulating PLCß and IP3R, partially reducing the apoptosis and promoting the proliferation of FA-treated spermatogenic cells. These findings revealed that GRPR participates in spermatogenesis through Ca2+ mediated by the PLCß/IP3R signaling pathway in FA-exposed rats.

Single-cell transcriptomic analysis of normal and pathological tissues from the same patient uncovers colon cancer progression.

The aim of the present study was to elucidate the evolutionary trajectory of colon cells from normal colon mucosa, to adenoma, then to carcinoma in the same microenvironment. Normal colon, adenoma and carcinoma tissues from the same patient were analyzed by single-cell sequencing, which perfectly simulated the process of time-dependent colon cancer due to the same microenvironment. A total of 22 cell types were identified. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in carcinoma. Epi1 and Entero0 were Co-enriched in antibacterial and IL-17 signaling, Entero5 was enriched in immune response and mucin-type O-glycan biosynthesis. We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified. We used colon samples from the same person, which provide new information for colon cancer therapy.

Study on TFF1 and PALB2 gene variants associated with gastric carcinoma risk in the Chinese Han population.

OBJECTIVE: Gastric carcinoma (GC) has received extensive attention due to its complex pathogenesis. Studies have shown that the expression of Trefoil factor 1 (TFF1) and Partner and localiser of BRCA2 (PALB2) genes promotes the occurrence of GC. Therefore, we investigated whether TFF1 and PALB2 gene polymorphisms are associated with GC risk in the Chinese Han population. METHODS: A total of 509 GC cases and 505 controls were recruited, and single nucleotide polymorphisms (SNPs) of TFF1 and PALB2 in these subjects were genotyped. The association between each candidate polymorphism and GC risk was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The visualization of gene-gene interactions and functional enrichment analysis were then performed using Cytoscape software and the R package "cluster profile". RESULTS: The TFF1 rs2156310 polymorphism significantly reduced the predisposition to GC in people under 60 years of age (AA vs. AG - GG, OR = 0.58, 95% CI = 0.35-0.97, p = 0.036). The gender-stratified analysis found that PALB2 rs513313 was significantly associated with the risk of GC in males (CT vs. TT, OR = 1.51, 95% CI = 1.06-2.15, p = 0.022). Besides, PALB2 rs249954 significantly reduced the susceptibility to GC in females (AA vs GG, OR = 0.42, 95% CI = 0.19-0.94, p = 0.034). CONCLUSION: Our results revealed that TFF1 and PALB2 gene polymorphisms were correlated with the genetic susceptibility to GC, providing certain data support for researchers to further study the mechanism of GC.

Integrated multi-omics profiling yields a clinically relevant molecular classification for esophageal squamous cell carcinoma.

Integrated molecular analysis of human cancer has yielded molecular classification for precise management of cancer patients. Here, we analyzed the whole genomic, epigenomic, transcriptomic, and proteomic data of 155 esophageal squamous cell carcinomas (ESCCs). Multi-omics analysis led to the classification of ESCCs into four subtypes: cell cycle pathway activation, NRF2 oncogenic activation, immune suppression (IS), and immune modulation (IM). IS and IM cases were highly immune infiltrated but differed in the type and distribution of immune cells. IM cases showed better response to immune checkpoint blockade therapy than other subtypes in a clinical trial. We further developed a classifier with 28 features to identify the IM subtype, which predicted anti-PD-1 therapy response with 85.7% sensitivity and 90% specificity. These results emphasize the clinical value of unbiased molecular classification based on multi-omics data and have the potential to further improve the understanding and treatment of ESCC.

WSP from "Nostoc commune" Vauch. suppresses gastric cancer migration via EGFRVIII signaling.

Introduction: A number of evidences have proved that "Nostoc commune" Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of "Nostoc commune" Vauch extracellular matrix- a water-stress protein (WSP) still needs to be elucidated. Methods: In our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment. Results: We found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells. Discussion: Given the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.

Clinical characteristics and outcomes of Castleman disease: a multicenter Consortium study of 428 patients with 15-year follow-up.

Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology for 215 patients (56.58%) and plasmacytic (PC) histopathology for 165 patients (43.42%). Most patients with UCD underwent surgical excision, whereas the treatment strategies of patients with iMCD were heterogeneous. The outcome for patients with UCD was better than that for patients with iMCD, 5-year overall survival (OS) rates were 95% and 74%, respectively. In further analysis, a multivariate analysis using a Cox regression model revealed that PC subtype, hepatomegaly and/or splenomegaly, hemoglobin ≤ 80 g/L, and albumin ≤ 30 g/L were independent prognostic factors of CD for OS. The model of iMCD revealed that age > 60 years, hepatomegaly and/or splenomegaly, and hemoglobin ≤ 80 g/L were independent risk factors. In UCD, single-factor analysis identified two significant risk factors: hemoglobin ≤ 100 g/L and albumin ≤ 30 g/L. Our study emphasizes the distinction of clinical characteristics between UCD and iMCD. The importance of poor risk factors of different clinical classifications may direct more precise and appropriate treatment strategies.

Characterization of somatic structural variations in 528 Chinese individuals with Esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) demonstrates high genome instability. Here, we analyze 528 whole genomes to investigate structural variations' mechanisms and biological functions. SVs show multi-mode distributions in size, indicating distinct mutational processes. We develop a tool and define five types of complex rearrangements with templated insertions. We highlight a type of fold-back inversion, which is associated with poor outcomes. Distinct rearrangement signatures demonstrate variable genomic metrics such as replicating time, spatial proximity, and chromatin accessibility. Specifically, fold-back inversion tends to occur near the centrosome; TD-c2 (Tandem duplication-cluster2) is significantly enriched in chromatin-accessibility and early-replication region compared to other signatures. Analyses of TD-c2 signature reveal 9 TD hotspots, of which we identify a hotspot consisting of a super-enhancer of PTHLH. We confirm the oncogenic effect of the PTHLH gene and its interaction with enhancers through functional experiments. Finally, extrachromosomal circular DNAs (ecDNAs) are present in 14% of ESCCs and have strong selective advantages to driver genes.

Semen Quality Following Long-term Occupational Exposure to Formaldehyde in China.

Importance: The potential effects of long-term occupational exposure to formaldehyde (FA) on human semen quality is not clear. Objective: To assess whether long-term occupational exposure to FA is associated with semen quality. Design, Setting, and Participants: This population-based cohort study was conducted from June 1 to June 30, 2021, in Xi'an, China. Participants were adults aged 23 to 40 years who had lived in the study area for 24 months or longer. Data analysis was performed from September 1 to October 1, 2021. Exposures: Long-term occupational exposure to FA was measured using a formaldehyde detector, and the FA exposure index (FEI) was calculated as follows: FEI = final concentration of FA (mg/m3) × work time during a workday (hour) × cumulative workdays (year). Main Outcomes and Measures: Semen samples were collected by masturbation after 3 to 7 days of abstinence and were then assessed by the computer-automated semen analysis system, Baso-Papanicolaou staining, and sperm-chromatin structure assay. Results: A total of 205 men (mean [SD] age, 29.49 [3.64] years), with 124 individuals in the FA exposure group (mean [SD] FEI, 73.72 [54.86]) and 81 age-matched controls, were included in the final analysis. Long-term personal occupational exposure to FA was significantly associated with poor semen quality. Specifically, a 1-unit increase in FEI was associated with a change of -0.99% (95% CI, -1.00% to -0.98%) in total sperm motility, -0.99% (95% CI, -0.99% to -0.97%) in progressive sperm motility, -0.05% (95% CI, -0.08% to -0.02%) in curvilinear velocity, -0.07% (95% CI, -0.10% to -0.04%) in straight line velocity, -0.07% (95% CI, -0.10% to -0.04%) in time-average velocity, -0.98% (95% CI, -0.99% to -0.93%) in normal sperm morphology, -0.24% (95% CI, -0.35% to -0.11%) in seminal neutral glucosidase, -0.61% (95% CI, -0.66% to -0.56%) in seminal plasma zinc, 0.52% (95% CI, 0.15% to 1.02%) in beat cross frequency, and 0.10% (95% CI, 0.06% to 0.14%) in the DNA fragmentation index. These associations remained significant after adjusting for confounding factors. Furthermore, subgroup analysis found that high levels of oxidative stress might promote the associations between FA exposure and semen quality. Conclusions and Relevance: This study found an association between long-term occupational exposure to FA and semen quality. This deterioration was dose and time dependent and might be induced by oxidative stress.

Analysis of albumin as a prognostic factor in HHV-8/HIV-negative Castleman disease from a multicenter study.

As a rare lymphoproliferative disorder, many patients with HHV-8/HIV-negative Castleman disease (CD) have hypoalbuminemia. However, data is limited on whether hypoalbuminemia is an independent predictor of CD. We retrospectively collected data from 230 patients diagnosed at 12 medical centers in China and the U.S. Different classifications included 147 patients with unicentric CD (UCD) and 83 with idiopathic multicentric CD (iMCD). Adjusted smooth curve fitting showed that the relationship between albumin and all-cause death of patients with CD and iMCD was linear. Cox proportional hazards regression modeling showed a negative association between the risk of death and albumin level (hazard ratio [HR]: 0.84; 95% CI, 0.76, 0.93). Using the Kaplan-Meier method, we determined that hypoproteinemia was a risk factor for poorer prognosis in patients with CD, UCD, and iMCD. Albumin was independently and negatively associated with the risk of death in CD patients, especially those with iMCD.

Serum urea acid and urea nitrogen levels are risk factors for maternal and fetal outcomes of pregnancy: a retrospective cohort study.

BACKGROUND: In recent years, results on the association between serum uric acid (UA) and pregnancy outcomes have been inconsistent, and the association between urea nitrogen (UN) and adverse pregnancy outcomes in normal pregnant women has not been reported. Thus, we examined the association of UA and UN levels during gestation with the risk of adverse pregnancy outcomes in a relatively large population. METHODS: A total of 1602 singleton mothers from Union Shenzhen Hospital of Huazhong University of Science and Technology at January 2015 to December 2018 were included. Both UA and UN levels were collected and measured during the second (16-18th week) and third (28-30th week) trimesters of gestation respectively. Statistical analysis was performed using multivariate logistic regression. RESULTS: After adjustment, the highest quartile of UA in the third trimester increased the risk of premature rupture of membranes (PROM) and small for gestational age infants (SGA) by 48% (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.04-2.10) and 99% (95% CI: 1.01-3.89) compared to those in the lowest quartile. The adjusted OR (95% CI) in the highest quartile of UN for the risk of SGA was 2.18 (95% CI: 1.16-4.13) and 2.29 (95% CI: 1.20-4.36) in the second and third trimester, respectively. In the second trimester, when UA and UN levels were both in the highest quartile, the adjusted OR (95% CI) for the risk of SGA was 2.51 (95% CI: 1.23-5.10). In the third trimester, when the group 1 (both indicators are in the first quartile) was compared, the adjusted ORs (95% CI) for the risk of SGA were 1.98 (95% CI: 1.22-3.23) and 2.31 (95% CI: 1.16-4.61) for group 2 (UA or UN is in the second or third quartile) and group 3 (both indicators are in the fourth quartile), respectively. CONCLUSIONS: Higher UA and UN levels increased the risk of maternal and fetal outcomes. The simultaneous elevation of UA and UN levels was a high-risk factors for the development of SGA, regardless of whether they were in the second or third trimester.

Adverse pregnancy outcomes are important public health problems in terms of high mortality and long-term health effects of maternal and newborn babies. This study assessed the association between serum urea acid and urea nitrogen levels during pregnancy and the risk of adverse pregnancy outcomes in Chinese women. The study was conducted between January 2015 and December 2018. Serum uric acid and urea nitrogen were measured at weeks 16­18 and 28­30, respectively. A total of 1602 singleton pregnant women participated in the study. We found that elevated levels of uric acid and urea nitrogen increased the risk of maternal and infant outcomes. In addition, we found for the first time that elevated uric acid and urea nitrogen concentrations were a risk factor for SGA, both in the second and third trimesters. Therefore, monitoring maternal uric acid and urea nitrogen biochemical parameters during pregnancy is necessary to optimize nursing and intervention. Furthermore, uric acid and urea nitrogen are simple, inexpensive, and readily available tests and should be evaluated additionally.

Association Between Serum Ferritin Concentration and Risk of Adverse Maternal and Fetal Pregnancy Outcomes: A Retrospective Cohort Study.

Objective: This study evaluated the associations of serum ferritin (SF) concentration during pregnancy with the risk of adverse maternal and fetal pregnancy outcomes. Methods: We conducted a retrospective study of 2327 pregnant women from 2015 to 2020 in Guangdong, China. SF concentrations were measured at 16-18th and 28-32th week of gestation. Logistic regression models were applied to estimate the association between SF concentration and the risk of adverse pregnancy outcomes. Results: After multivariable adjustment, the odds ratio (OR) of the highest quartile of SF concentration at 16-18th week of gestation was 1.43 (95% confidence interval [CI]: 1.09, 1.89) for gestational diabetes mellitus (GDM) and 1.79 (95% CI: 1.15, 2.79) for small for gestational age (SGA) when compared with the lowest quartile. At 28-32th week of gestation compared with the lowest quartile, women with SF in the highest quartile had an increased risk of SGA (OR: 1.62; 95% CI: 1.01, 2.62). Moreover, the lowest quartile of SF concentration decreased risk of SGA by 90% (95% CI: 0.01, 0.80) when compared with the highest quartile among pregnancy women with GDM. Conclusion: Elevated SF concentrations increased the risk of GDM and SGA during pregnancy. Maintaining an appropriately low level of maternal SF at 28-32th week of gestation in women with GDM could reduce the risk of SGA.

Rno_circRNA_008646 regulates formaldehyde induced lung injury through Rno-miR-224 mediated FOXI1/CFTR axis.

Formaldehyde (FA) serves as a prevailing air pollutant, which has seriously threatened public health in recent years. Of all the known health effects, lung injury is one of the most severe risks. However, little is known about the circRNAs related molecular mechanism in the development of lung injury induced by FA. This study was designed to explore the potential roles of dysregulated circRNAs as well as its mechanism in FA-induced lung injury. In the present study, 24 male SD rats were exposed to formaldehyde (control, 0.5, 2.46 and 5 mg/m3) for 8 h per day for 8 weeks to induce lung injury. We used H&E staining to evaluate the histopathological changes of lung injury indifferent groups. The expression of circRNAs in lung tissue was detected by real-time PCR. Meanwhile, circRNA/miRNA/mRNA interaction networks were predicted by bioinformatics analysis. Our study revealed that formaldehyde exposure resulted in abnormal histopathological changes in lung tissues. Moreover, the expression of rno_circRNA_008646 was significantly higher in lung tissues of formaldehyde exposure rats than in control. Bioinformatics analysis showed that one potential target miRNA/mRNA for rno_circRNA_008646 was rno-miR-224/Forkhead Box I1 (FOXI1). Besides, luciferase report gene confirmed that there was targeted binding relationship between rno_circRNA_008646 and rno-miR-224, rno-miR-224 and FOXI1. Further verification experiments indicated that the expression of rno_circRNA_008646 was negatively correlated rno-miR-224, while it was positively correlated with FOXI1. JASPAR database showed transcription factor FOXI1 located in promotor of CF Transmembrane Conductance Regulator (CFTR). Both FOXI1 and CFTR were up-regulated in lung tissues after formaldehyde exposure. In conclusion, our findings suggested that formaldehyde may induce lung injury, and this may be caused by up-regulatedrno_circRNA_008646, which medicated rno-miR-224/FOXI1/CFTR axis.

FOCAD/miR-491-5p, downregulated by EGR1, function as tumor suppressor by inhibiting the proliferation and migration of gastric cancer cells.

Gastric cancer is a common malignant tumor in China; however, its carcinogenesis remains unknown. Focadhesin (FOCAD) is a tumor suppressor gene in gliomas, its expression, role, and mechanism in gastric cancer have not been defined. The aim of the present study was to explore the expression pattern of FOCAD in human normal tissues and cancer tissues and elucidate the role and regulatory mechanism of Early Growth Response 1 (EGR1) in FOCAD and its intron, miR-491-5p, in gastric cancer. Immuno histochemical staining revealed that FOCAD is widely and highly expressed in normal gastric mucosa, but is absent in gastric cancer tissue. Based on an association analysis FOCAD expression was found to be negatively associated with lymph node metastasis (P = 0.004); higher FOCAD levels were associated with longer survival in patients with gastric cancer (P = 0.001). MTT, colony, Transwell chamber, and flow cytometry assays revealed that siFOCAD promoted cell proliferation, growth, and migration, and inhibited apoptosis. Furthermore, bioinformatic analysis, Fluorescence reporter gene and chromatin immunoprecipitation analyses confirmed that EGR1 binds to the promoter and negatively regulates FOCAD and miR-491-5p at the transcriptional level. The overexpression of EGR1 was also found to promote cell proliferation, growth, and migration, and inhibit apoptosis. Overall, FOCAD is specifically overexpressed in the gastric mucosa and is significantly downregulated in gastric cancer. To our knowledge, this is the first study to demonstrate that FOCAD is a tumor suppressor, higher FOCAD levels might be a better prognostic marker of gastric cancer, and FOCAD/miR-491-5p may be negatively regulated by EGR1.

MBD1/HDAC3-miR-5701-FGFR2 axis promotes the development of gastric cancer.

Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide due to the lack of specific biomarkers for the early diagnosis and universal accepted therapy for advanced GC. Lower levels of miR-5701 were found in the GC tissue from the online sequencing data and confirmed in the GC tissues and GC cell lines. Overexpression of miR-5701 inhibited the proliferation and migration of GC cells and promoted the apoptosis of these cells. Bioinformatics analyses and luciferase assay showed that miR-5701 targeted FGFR2, which acted as an oncogene in GC. Nude mice with GC cells overexpressing miR-5701 exhibited smaller tumor sizes and less lung metastases. The miR-5701 expression was directly, transcriptionally inhibited by MBD1 together with HDAC3 by binding together to form a complex. Knocked down MBD1 or HDAC3 increased the miR-5701 expression. These results indicated the potential use of exogenously administered miR-5701 or agents that elevated endogenous miR-5701 to inhibit GC, improving the prognosis of patients with GC.