The long noncoding RNA TARID regulates the CXCL3/ERK/MAPK pathway in trophoblasts and is associated with preeclampsia.

BACKGROUND: The widely accepted explanation of preeclampsia (PE) pathogenesis is insufficient trophoblast invasion and impaired uterine spiral artery remodeling. However, the underlying molecular mechanism remains unclear. METHODS: We performed transcriptome sequencing on placentas of normal and PE patients and identified 976 differentially expressed long noncoding RNAs (lncRNAs). TCF21 antisense RNA inducing demethylation (TARID) was one of the most significantly differentially expressed lncRNAs and was negatively correlated with the systolic and diastolic blood pressure in PE patients. Furthermore, we verified the effect of TARID on the biological behavior of trophoblasts and performed UID mRNA-seq to identify the effectors downstream of TARID. Then, co-transfection experiments were used to better illustrate the interaction between TARID and its downstream effector. RESULTS: We concluded that the downregulation of TARID expression may inhibit trophoblast infiltration and spiral artery remodeling through inhibition of cell migration, invasion, and tube formation mediated through the CXCL3/ERK/MAPK pathway. CONCLUSIONS: Overall, these findings suggested that TARID may be a therapeutic target for PE through the CXCL3/ERK/MAPK pathway.

Integrated Bioinformatics Analysis for the Identification of Key Molecules and Pathways in the Hippocampus of Rats After Traumatic Brain Injury.

High-throughput and bioinformatics technology have been broadly applied to demonstrate the key molecules involved in traumatic brain injury (TBI), while no study has integrated the available TBI-related datasets for analysis. In this study, four available expression datasets of fluid percussion injury (FPI) and sham samples from the hippocampus of rats were analysed. A total of 248 differentially expressed genes (DEGs) and 10 differentially expressed microRNAs (DEMIs) were identified. Then, functional annotation was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Most of the DEGs were enriched for the term inflammatory immune response. The MCODE plug-in in the Cytoscape software was applied to build a protein-protein interaction (PPI) network, and 18 hub genes were demonstrated to be enriched in the cell cycle pathway. Besides, time sequence (3 h, 6 h, 12 h, 24 h, and 48 h) profile analysis was performed using short time-series expression miner (STEM). The significantly expressed genes were assigned into 24 pattern clusters with four significant uptrend clusters. Four DEGs, Fcgr2a, Bcl2a1, Cxcl16, and Gbp2, were found to be differentially expressed at all time-points. Fifty-three DEGs and eight DEMIs were identified to form a miRNA-mRNA negative regulatory network using miRWalk3.0 and Cytoscape. Moreover, the mRNA levels of eight hub genes were validated by qRT-PCR. These DEGs, DEMIs, and time-dependent expression patterns facilitate our knowledge of the molecular mechanisms underlying the process of TBI in the hippocampus of rats and have the potential to improve the diagnosis and treatment of TBI.

A functional variant in the flanking region of pri-let-7f contributes to colorectal cancer risk in a Chinese population.

Let-7f was reported to be downregulated in patients with colorectal cancer (CRC). However, little is known about the role of let-7f in CRC carcinogenesis. The aim of this study was to investigate the correlation between genetic polymorphisms in the flanking region of pri-let-7f and CRC risk, as well as the potential role of let-7f in CRC cell migration and invasion. The pri-let-7f-1 rs10739971 and pri-let-7f-2 rs17276588 were genotyped using TaqMan (Applied Biosystems, Foster City, CA) assay. The luciferase activity was detected using Dual-Luciferase Reporter Assay. CRC cell migration and invasion were evaluated using transwell chamber assay. The rs17276588 AG and AG/AA genotypes had a significantly increased CRC risk (AG vs. GG: adjusted odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.19-1.83, p < 0.001; AG/AA vs. GG: adjusted OR = 1.43, 95% CI = 1.17-1.75, p < 0.001). Stratification analyses showed that the increased risk was observed in CRC patients with well-moderately differential status, patients with clinical Stages I-II, and patients without lymph node metastasis. The rs17276588A allele displayed a decreased transcriptional activity and low levels of let-7f. Moreover, let-7f inhibited migration and invasion in Caco-2 and Lovo cells. These findings indicate that the rs17276588 AG/AA genotypes increased CRC risk by reducing the expression of tumor suppressor let-7f.

Epigenetic modifications but not genetic polymorphisms regulate KEAP1 expression in colorectal cancer.

Kelch-like ECH-associated protein 1 (KEAP1), as a negative regulator of nuclear factor erythroid 2 like 2 ( NRF2), plays a pivotal role in NRF2 signaling pathway and involves in tumorigenesis. Polymorphisms and methylation in gene promoter region may influence its expression and be related to cancer susceptibility. In this study, we examined the effect of the KEAP1-NRF2 interaction on the risk of colorectal cancer (CRC). The polymorphisms of NRF2 and KEAP1 were genotyped using the improved multiplex ligase detection reaction assay. KEAP1 promoter methylation and histone modification were analyzed using bisulfite genome sequencing and chromatin immunoprecipitation (ChIP) assay, respectively. The KEAP1 rs1048290 CC genotype and C allele were associated with increased risks of CRC (CC vs GG: odds ratio [OR] = 1.39; 95% confidence interval [CI], 1.08-1.78; CC vs GG/GC: OR = 1.29; 95% CI, 1.05-1.58; C vs G: OR = 1.18; 95% CI, 1.04-1.34). The rs1048290-rs11545829 GT haplotype was associated with a reduced risk of CRC. KEAP1-NRF2 interaction analysis revealed that the rs6721961, rs35652124, rs1048290, and rs11545829 conferred the susceptibility to CRC. The hypermethylation of KEAP1 promoter resulted in lower levels of KEAP1 messenger RNA (mRNA). After treatment with 5-aza-2'-deoxycytidine/trichostatin A, KEAP1 promoter methylation was decreased and KEAP1 mRNA levels were increased. ChIP-quantitative polymerase chain reaction results showed an enhanced enrichment of H3K4Me3 and H3K27Ac to the promoter of KEAP1. In vitro methylation analysis showed that the methylated plasmid decreased the transcriptional activity by 70%-84%. These findings suggest that the KEAP1- NRF2 pathway could potentially impact CRC risk and the downregulation of KEAP1 could be explained in part by epigenetic modifications.

DNA methylome and transcriptome alterations and cancer prevention by curcumin in colitis-accelerated colon cancer in mice.

Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in azoxymethane-dextran sulfate sodium (AOM-DSS) mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anticancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed. We identified lists of differentially expressed and differentially methylated genes in pairwise comparisons and several pathways involved in the potential anticancer effect of curcumin. These pathways include LPS/IL-1-mediated inhibition of RXR function, Nrf2-mediated oxidative stress response, production of NO and ROS in macrophages and IL-6 signaling. Among these genes, Tnf stood out with decreased DNA CpG methylation of Tnf in the AOM-DSS group and reversal of the AOM-DSS induced Tnf demethylation by curcumin. These observations in Tnf methylation correlated with increased and decreased Tnf expression in RNA-seq. The functional role of DNA methylation of Tnf was further confirmed by in vitro luciferase transcriptional activity assay. In addition, the DNA methylation level in a group of inflammatory genes was decreased in the AOM+DSS group but restored by curcumin and was validated by pyrosequencing. This study shows for the first time epigenomic changes in DNA CpG methylation in the inflammatory response from colitis-associated colon cancer and the reversal of their CpG methylation changes by curcumin. Future clinical epigenetic studies with curcumin in inflammation-associated colon cancer would be warranted.

The triterpenoid corosolic acid blocks transformation and epigenetically reactivates Nrf2 in TRAMP-C1 prostate cells.

Corosolic acid (CRA) is found in various plants and has been used as a health food supplement worldwide. Although it has been reported that CRA exhibits significant anticancer activity, the effect of this compound on prostate cancer remains unknown. In this study, we investigated the effect of CRA on cellular transformation and the reactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) through epigenetic regulation in TRAMP-C1 prostate cells. Specifically, we found that CRA inhibited anchorage-independent growth of prostate cancer TRAMP-C1 cells but not Nrf2 knockout prostate cancer TRAMP-C1 cells. Moreover, CRA induced mRNA and protein expression of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H Quinone Oxidoreductase 1 (NQO1). Bisulfite genomic sequencing and methylated DNA immunoprecipitation results revealed that CRA treatment decreased the level of methylation of the first five CpG sites of the Nrf2 promoter. Histone modification was analyzed using a chromatin immunoprecipitation (ChIP) assay, which revealed that CRA treatment increased the acetylation of histone H3 lysine 27 (H3K27ac) while decreasing the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter region of Nrf2. Furthermore, CRA treatment attenuated the protein expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). These findings indicate that CRA has a significant anticancer effect in TRAMP-C1 cells, which could be partly attributed to epigenetics including its ability to epigenetically restore the expression of Nrf2.

Curcumin Derivative Epigenetically Reactivates Nrf2 Antioxidative Stress Signaling in Mouse Prostate Cancer TRAMP C1 Cells.

The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-bis-(3,4,5-trimethoxybenzylidene)-tetrahydro-thiopyran-4-one (F10) and (3E,5E)-3,5-bis-(3,4,5-trimethoxy-benzylidene)-tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin, and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways. We performed real-time quantitative PCR and Western blotting to investigate the effects of F10 and E10 on Nrf2, correlated phase II detoxification genes. We also measured expression and activity of DNMTand HDAC enzymes. Enrichment of H3K27me3 on the promoter region of Nrf2 was explored with a chromatin immunoprecipitation (ChIP) assay. Methylation of the CpG region in Nrf2 promoter was doubly examined by bisulfite genomic sequencing (BGS) and methylation DNA immunoprecipitation (MeDIP). Compared with curcumin and SFN, F10 is more potent in activating Nrf2-ARE pathways. Both F10 and E10 enhanced level of Nrf2 and the correlated phase II detoxifying genes. BGS and MeDIP assays indicated that F10 but not E10 hypomethylated the Nrf2 promoter. F10 also downregulated the protein level of DNMT1, DNMT3a, DNMT3b, HDAC1, HDAC4, and HDAC7 and the activity of DNMTs and HDACs. F10 but not E10 effectively reduced the accumulation of H3k27me3 on the promoter of Nrf2. F10 and E10 can activate the Nrf2-ARE pathway and increase the level of Nrf2 and correlated phase II detoxification genes. The reactivation effect on Nrf2 by F10 in TRAMP C1 may come from demethylation, decrease of HDACs, and inhibition of H3k27me3 accumulation.

Combined analysis of pri-miR-34b/c rs4938723 and TP53 Arg72Pro with cervical cancer risk.

miR-34 family members can form a p53-miR-34 positive feedback loop and induce apoptosis, DNA repair, angiogenesis, and cell cycle arrest. We conducted a case-control study to examine whether two polymorphisms (i.e., rs4938723 in the promoter of pri-miR-34b/c and TP53 Arg72Pro) were linked to the carcinogenesis of cervical cancer among Chinese Han women. Genotypes of the two polymorphisms in 328 cervical cancer patients and 568 control subjects were determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. We found a significantly increased cervical cancer risk in the pri-miR-34b/c rs4938723 under dominant and overdominant model (CT/CC vs. TT: adjusted OR = 1.34, 95 % CI = 1.01-1.77; CT vs. TT/CC: adjusted OR = 1.37, 95 % CI = 1.05-1.80, respectively). Increased cervical cancer risks were also found in the TP53 Arg72Pro under a heterozygous comparison and overdominant model (CG vs. GG: adjusted OR = 1.44, 95 % CI = 1.06-1.95; CG vs. GG/CC: adjusted OR = 1.47, 95 % CI = 1.12-1.94, respectively). Stratification analysis showed that patients carrying the pri-miR-34b/c rs4938723 CT genotype had a significantly increased risk for developing poorly differential status and clinical stage I. Moreover, increased cancer risks were observed for the TP53 Arg72Pro polymorphism in patients with poorly differential status, clinical stage II, and without lymph node metastasis. Combined analysis revealed that the genotypes of rs4938723 CT/CC and TP53 Arg72Pro CG/CC had an increased cervical cancer risk (OR = 2.21, 95 % CI = 1.38-3.53). These findings suggest that the pri-miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms may contribute to the genesis of cervical cancer.

Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of gastric cancer.

A long ncRNA (lncRNA) prostate cancer non-coding RNA 1 (PRNCR1) in the 8q24 has been reported to be upregulated in prostate cancer with a function of activating androgen receptor (AR). AR plays a key role in the gender disparity, cell migration, and invasion of gastric cancer (GC). We hypothesized that single nucleotide polymorphisms (SNPs) in the lncRNA PRNCR1 may be related to the risk of GC. We conducted a case-control study to investigate the association between SNPs in the lncRNA PRNCR1 and the risk of GC. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to determine the genotypes of 613 subjects including 219 cases with GC and 394 controls. We found that patients with the rs13252298AG genotype displayed a 1.50-fold increased risk of GC (AG vs. AA, 95 % confidence interval (CI) = 1.05-2.12, p = 0.02). Interestingly, the rs7007694CT and CC and the rs1456315GG genotypes displayed a decreased risk of GC (rs7007694CT vs. TT, odds ratio (OR) = 0.68, 95 % CI = 0.48-0.97, p = 0.03; rs7007694CC vs. TT, OR = 0.36, 95 % CI = 0.13-0.97, p = 0.04; rs1456315GG vs. AA, OR = 0.30, 95 % CI = 0.13-0.70, p = 0.004, respectively). Our results suggest that SNPs in the lncRNA PRNCR1 may be a biomarker for the etiology of GC.

Interaction analysis of IL-12A and IL-12B polymorphisms with the risk of colorectal cancer.

IL-12 is an antitumor cytokine with functions of inhibiting tumor growth, invasion, and metastasis, indicating that IL-12 is a promising candidate for cancer treatment. The aim of this study was to investigate the association of IL-12A rs568408, IL-12A rs2243115, and IL-12B rs3212227 with the susceptibility to colorectal cancer (CRC). Two hundred and fifty-seven histopathologically confirmed CRC patients and 236 age- and gender-matched controls were enrolled. The three polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. We found that the IL-12A rs568408 AG/AA genotypes were associated with an increased risk of CRC with an adjusted odds ratio (OR) of 1.66 (95 % confidence interval (CI), 1.11-2.48). Stratified analyses showed that patients carrying the IL-12B rs3212227AC/CC genotypes had a 1.97-fold increased risk of tumor metastasis (OR = 1.97; 95 % CI, 1.04-3.70). Gene-gene interaction analysis showed that subjects carrying the IL-12A rs568408AG/AA and IL-12B rs3212227AA genotypes had a 2.40-fold increased risk of CRC (OR = 2.40; 95 % CI, 1.14-5.07) and individuals carrying the IL-12A rs568408AG/AA and IL-12B rs3212227AC/CC genotypes had a 1.93-fold increased risk of CRC (OR = 1.93; 95 % CI, 1.10-3.41). These findings indicate that IL-12A rs568408 and IL-12B rs3212227 may be related to the development of CRC.

A let-7 KRAS rs712 polymorphism increases colorectal cancer risk.

Growing evidence has indicated that polymorphism present in the miRNA binding site of target gene can alter the ability of miRNAs to bind its target gene and modulate the development and progression of cancer. We aimed to investigate the association between let-7 KRAS rs712 polymorphism and the risk of colorectal cancer (CRC). The let-7 KRAS rs712 was analyzed in a case-control study, including 339 CRC patients and 313 age- and sex-matched controls; the relationship between the polymorphism and the clinicopathological features of CRC was also examined. Individuals carrying the let-7 KRAS rs712 TT genotype and T allele had an increased risk of developing CRC (TT vs. GG, adjusted OR = 2.18; 95% CI, 1.00-4.77; T vs. G, adjusted OR = 1.50; 95% CI, 1.15-1.96). Stratified analyses revealed that CRC patients with the let-7 KRAS rs712 TT genotype were more likely to have clinical stage III or IV disease (OR = 3.29, 95% CI, 1.32-8.20) and distant metastasis (OR = 4.70, 95% CI, 1.81-12.25). These findings provide evidence that the let-7 KRAS rs712 polymorphism may play crucial roles in the etiology of CRC.

Association between a functional insertion/deletion polymorphism in IL1A gene and risk of papillary thyroid carcinoma.

The aim of this study was to evaluate whether an insertion/deletion polymorphism (rs3783553) locating in the miR-122 target gene IL1A 3' untranslated region was related to the risk of papillary thyroid carcinoma (PTC). Genomic DNA was extracted from peripheral venous blood of 273 patients with PTC and 509 controls. The IL1A rs3783553 polymorphism was genotyped by using a polymerase chain reaction assay. No significant difference of the distribution of the IL1A rs3783553 polymorphism was observed between PTC patients and controls. However, patients carrying the IL1A rs3783553 ins/ins genotype and ins allele had significantly decreased risks for developing T3 and T4 when compared with patients carrying the IL1A rs3783553 del/del genotype and del allele (ins/ins vs. del/del: OR = 0.22, 95% confidence interval (CI), 0.09-0.54; ins vs. del: OR = 0.58, 95% CI, 0.41-0.83, respectively). These results suggest that the rs3783553 polymorphism may be used as a genetic marker to predict the size/extension of PTC.

Microneedle-mediated drug delivery for neurological diseases.

Neurological disorders, including brain injury, brain tumors, and neurodegenerative diseases, rank as the second leading cause of death worldwide. Exploring effective new treatments for neurological disorders has long been a hot research issue in clinical practice. Recently, microneedles (MNs) have attracted much attention due to their designation as a "painless and non-invasive" novel transdermal delivery method, characterized by their biocompatibility and sustainability. The advantages of MNs open an avenue for potential therapeutic interventions targeting neurological disorders. This review presents a concise overview of progress in the field of MNs, with highlights on the application in the treatment of neurological disorders. Notably, trends in the development of MNs and future challenges are also discussed.

A portable all-in-one microfluidic device with real-time colorimetric LAMP for HPV16 and HPV18 DNA point-of-care testing.

Screening for high-risk human papillomavirus (HPV) infection is one of the most important preventative measures for cervical cancer. However, fast, convenient, and low-cost HPV detection remains challenging, especially in resource-limited settings. Here, we report a portable all-in-one device (PAD) for point-of-care testing (POCT) for HPV16 and HPV18 DNA in cervical swabs. The PAD was engineered to integrate modules for extraction-free sample lysis, loop-mediated isothermal amplification (LAMP) with lyophilized reagent beads, and real-time colorimetric signal sensing into a single miniaturized device, considerably shortening the sample-to-result time to 15 min. The precision liquid handling in the completely sealed microfluidic chip is achieved by a uniquely designed pressure-balanced automatic liquid flow mechanism, thereby eliminating the need for manual manipulation of liquids and thus the risk of biohazards. The PAD employs an improved real-time colorimetric LAMP (rcLAMP) assay with a limit of detection (LOD) of 1 copy/µL, enabled by enhanced assay chemistry to maximize the reaction kinetics. To validate this device for clinical application, we tested 206 clinical cervical swab samples and obtained a sensitivity of 92.1% and a specificity of 99.0%. This custom PAD enabled by microfluidic and electronic engineering techniques can be configured for the simultaneous detection of HPV16 and HPV18 or other pathogens in point-of-care applications.

A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer.

The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs TP53-mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-miR-34b/c was predicted to influence the GATA-X binding sites. We aimed to investigate the association between miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of CRC. We genotyped the two polymorphisms in 347 CRC patients and 488 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of CRC compared with the TT genotype and T allele (CC vs. TT: adjusted OR=0.56; 95% CI, 0.34-0.91; C vs. T: adjusted OR=0.78; 95% CI, 0.64-0.97). In combined analysis, a borderline significance was also observed in subjects carrying the rs4938723 CT/CC and TP53 GG genotypes (adjusted OR=0.66; 95% CI, 0.43-0.99). These findings indicate that the rs4938723 in the promoter region of pri-miR-34b/c was a protective factor for the development of CRC. As the significance is marginal, further replication studies are warranted to confirm these results.

Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma.

Growing evidence indicates that tumor suppressor gene TP-53 and non-coding RNA miR-34b/c independently and/or jointly play crucial roles in carcinogenesis. We hypothesized that the polymorphisms of rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72-Pro may be related to the risk of nasopharyngeal carcinoma (NPC). We performed a case-control study between 217 patients with NPC and 360 healthy controls in a Chinese population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A significantly increased risk of NPC was observed in the miR-34b/c rs4938723 CT/CC genotypes compared with the TT genotype (adjusted OR=1.44, 95 % CI 1.02-2.03, p=0.04), and also the C allele (adjusted OR=1.33, 95 % CI 1.04-1.70, p=0.03). The gene-gene interaction of miR-34b/c rs4938723 and TP-53 Arg72-Pro showed that the combined genotypes of rs4938723CT/CC and TP-53CG/CC increased the risk of NPC (rs4938723CT/CC + TP-53CG/CC vs. rs4938723 TT+TP-53 CG/CC: OR=1.58, 95 % CI 1.04-2.42, p=0.03). These findings suggest that miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may singly or collaboratively contribute to the risk of NPC.

A let-7 binding site polymorphism rs712 in the KRAS 3' UTR is associated with an increased risk of gastric cancer.

Recently, single nucleotide polymorphisms in let-7 miRNA binding site in 3' untranslated region (UTR) of KRAS mRNA have been found to be associated with the cancer risk. In this study, we genotyped the frequency of KRAS rs712 to test its effect on gastric cancer (GC) risk in a hospital-based case-control study in a Chinese population, with 181 histologically confirmed GC patients and 674 cancer-free controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The TT genotype of rs712 was associated with an increased risk of GC when taking GG genotype as a reference (adjusted odds ratio (OR) = 3.05, 95 % confidence interval (CI), 1.53-6.08). Similarly, the T allele of rs712 was associated with a statistically significant increase in susceptibility compared with G allele (adjusted OR = 1.44, 95 % CI, 1.10-1.90). Our data demonstrated that the T allele of the let-7 binding site polymorphism rs712 in KRAS 3' UTR was associated with a significantly increased risk of GC, suggesting that the KRAS rs712 polymorphism may be a genetic marker for the development of GC.

Clinical evaluation of soluble intercellular adhesion molecule-1 and insulin like growth factor-binding protein-1-based rapid immunoassays for the diagnosis of prelabor rupture of membranes.

AIMS: To evaluate the clinical value of two rapid tests, based on soluble intercellular adhesion molecule-1 (Leakection) and insulinlike growth factor-binding protein-1 (Amnioquick), for the diagnosis of prelabor rupture of membranes. METHODS: A total of 200 pregnant women were recruited in this study: 100 pregnant women with membrane rupture and 100 healthy pregnant women as controls. Patients and controls were randomly divided into Leakection and Amnioquick groups, respectively. Sensitivity and specificity were calculated on the basis of the detection results. RESULTS: For the 100 women tested with Leakection, the sensitivity and specificity was 94% and 96%, respectively; the total accuracy was 95%. For the 100 women tested with Amnioquick, the sensitivity and specificity was 80% and 100%, respectively; the total accuracy was 90%. CONCLUSIONS: Both Leakection and Amnioquick are noninvasive and inexpensive rapid tests for the diagnosis of premature or prelabor rupture of membranes with high sensitivity and specificity. These tests could greatly help the timely diagnosis of premature or prelabor rupture of membranes in clinical practice.

[Expression of SSB following early myocardial ischemia in rats].

OBJECTIVE: To investigate the expression of Sjögren's syndrome antigen B (SSB) gene and SSB protein in the early ischemic myocardium in rats. METHODS: Adult healthy Sprague-Dawley rats were randomly divided into groups of operation [myocardial ischemia (MI) and non-ischemia (NI)], non-operation (NO) and sham-operation (SO) (n = 6 for MI and NI; n = 4 for NO and SO). According to time of ischemia, it was then divided into groups of 0 min, 15 min, 30 min, 60 min, 120 min, and 240 min. The expression of SSB gene in the myocardium was examined by real-time PCR, and the expression of SSB protein was examined by Western blot and immunofluorescence staining. RESULTS: The expressions of SSB gene was down-regulated at early stage of ischemia. There was significant difference between 0 min and 120 min at the level of expression of SSB gene in MI group, so did that between 120 min group and NO group (P < 0.05). The expression of SSB protein at 60 min after ischemia was significantly decreased compared with that in the group of 0 min (P < 0.05). The expression of SSB protein in NI groups was significantly higher than that in MI groups at the time of 60 min and 120 min after myocardial ischemia (P < 0.05). Additionally, the expression of SSB protein was mainly located in the myocardial nucleus, myocardial plasma, and plasma membrane of partial myocardiocytes according to the result of immunofluorescence staining. CONCLUSION: SSB may participate in pathophysiologic regulation process in myocardial cells at the early stage of myocardial ischemia in rats.

Insights into Enhancer RNAs: Biogenesis and Emerging Role in Brain Diseases.

Enhancers are cis-acting elements that control the transcription of target genes and are transcribed into a class of noncoding RNAs (ncRNAs) termed enhancer RNAs (eRNAs). eRNAs have shorter half-lives than mRNAs and long noncoding RNAs; however, the frequency of transcription of eRNAs is close to that of mRNAs. eRNA expression is associated with a high level of histone mark H3K27ac and a low level of H3K27me3. Although eRNAs only account for a small proportion of ncRNAs, their functions are important. eRNAs can not only increase enhancer activity by promoting the formation of enhancer-promoter loops but also regulate transcriptional activation. Increasing numbers of studies have found that eRNAs play an important role in the occurrence and development of brain diseases; however, further research into eRNAs is required. This review discusses the concept, characteristics, classification, function, and potential roles of eRNAs in brain diseases.