Search

Physiological electric fields (EFs), as one of the environmental cues influencing both normal and tumor cells, have profound effects on tumor cell malignancy potential. The cellular responses to EFs by choriocarcinoma cells and their underlying mechanisms are unknown. In this study, the migration/motility, cell cycle progression and proliferation of choriocarcinoma cells in electric field culture showed that choriocarcinoma cells migrated cathodally in an applied EF, and EF stimulation influenced cell cycle progression through G2/M arrest and therefore induced a reduction in cellular proliferation. The transcriptome of choriocarcinoma cells subjected to EF stimulation (150 mV/mm) was analyzed using RNA sequencing (RNA-Seq), and the results were verified by reverse transcription quantitative polymerase chain reaction. A Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that ErbB and HIF-1 signaling pathways that are involved in cell migration/motility, cell cycle progression and proliferation were significantly altered in cells treated with an EF of 150 mV/mm compared with control cells, and in addition, the downstream pathways of these signaling pathways such as AKT and P42/P44 MAPK (ERK1/2) showed primary activation by Western blotting. This study's results suggest that an applied EF is an effective cue in regulating cellular phenotypes of choriocarcinoma cells and that transcriptional analysis contributes to the understanding of the mechanism of EF-guided cell functions.

Nicotine addiction and the occurrence of lymph node spread are two major significant factors associated with esophageal cancer’s poor prognosis; however, nicotine’s role in inducing lymphatic metastasis of esophageal cancer remains unclear. Here we show that OTU domain-containing protein 3 (OTUD3) is downregulated by nicotine and correlates with poor prognosis in heavy-smoking esophageal cancer patients. OTUD3 directly interacts with ZFP36 ring finger protein (ZFP36) and stabilizes it by inhibiting FBXW7-mediated K48-linked polyubiquitination. ZFP36 binds with the VEGF-C 3-‘UTR and recruits the RNA degrading complex to induce its rapid mRNA decay. Downregulation of OTUD3 and ZFP36 is essential for nicotine-induced VEGF-C production and lymphatic metastasis in esophageal cancer. This study establishes that the OTUD3/ZFP36/VEGF-C axis plays a vital role in nicotine addiction-induced lymphatic metastasis, suggesting that OTUD3 may serve as a prognostic marker, and induction of the VEGF-C mRNA decay might be a potential therapeutic strategy against human esophageal cancer., The mechanism of how VEGF-C is regulated to promote lymphatic metastasis of oesophageal cancer is unclear. Here the authors show that nicotine prevents the mRNA decay of VEGF-C mRNA and promotes lymphatic metastasis by downregulating deubiquitinase OTUD3 and RNA binding protein ZFP36.

Accumulating evidence indicates that circular (circ)RNAs exhibit complex functions in diverse malignant tumors, including non‑small cell lung cancer (NSCLC). The role of the circRNA transcription adaptor 2A (circTADA2A) in NSCLC remains unclear. The expression, function and mechanism of circTADA2A in NSCLC development were investigated in the present study. The results revealed that circTADA2A was upregulated in NSCLC, and that knockdown of circTADA2A inhibited cell proliferation and migration in the NSCLC cell lines A549 and H1299. Functional assays demonstrated that circTADA2A promoted proliferation and migration via interacting with microRNA (miR)‑638. Bioinformatics and reverse transcription‑quantitative PCR assay confirmed that miR‑638 was expressed at low levels in NSCLC. In addition, it was found that miR‑638 served a tumor‑suppressive role and suppressed proliferation and migration via PCNA clamp associated factor (KIAA0101) inhibition in A549 and H1299 cells. Lastly, it was verified that circTADA2A promoted cell proliferation and migration, at least partially, via miR‑638/KIAA0101 signaling in A549 and H1299 cells. In summary, the present study showed that circTADA2A promoted NSCLC cell proliferation and migration via modulating miR‑638/KIAA0101 signaling.

GALNT2 is a GalNAc transferase that regulates insulin signaling, lipogenesis, and serum lipid fractions. The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of polycystic ovary syndrome (PCOS) and related traits. The two SNPs were genotyped in 616 PCOS patients and 482 control subjects. Genetic associations with related traits were also analyzed. The genotype distributions of the two SNPs in PCOS patients were similar to those of normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables. In the PCOS group, subjects with genotype AA at the rs4846914 SNP exhibited an increased fasting serum insulin and homeostasis model insulin resistance (HOMA-IR) index compared with that of corresponding GG or GA genotype carriers (all P

Context and objective Preeclampsia is a pregnancy-specific disorder associated with pro-inflammatory and pro-thrombotic events. The growth arrest-specific 6 (GAS6) has been implicated in systemic inflammation and coagulation. Common genetic polymorphisms of GAS6 gene have previously been reported. The aim of this study was to investigate the association of GAS6 gene polymorphisms with the risk of preeclampsia in Chinese subjects. Study design The case–control population consists of 551 subjects. The genotyping of the single-nucleotide polymorphisms of GAS6 gene, GAS6 834 +7G/A(rs8191974) and +1332C/T (rs1803628), was carried out on genomic DNA using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis. Results There were significant differences in the +1332C/T genotype and allele frequencies between the patients with preeclampsia and the controls (P=0.03 and 0.02, respectively). The +1332 TT genotype was found to be protective from the development of preeclampsia (odds ratios 0.271, 95% confidence interval 0.077–0.953; P=0.03). Further analysis showed that the TT genotype of the GAS6 +1332C/T conferred a risk of severe preeclampsia (OR=0.597, 95% confidence interval 0.416–0.855; P=0.01). However, there were no differences in the 834+7G/A genotype and allele frequencies between the patients with preeclampsia and the controls. Conclusion Our data suggest that a TT genotype at +1332C/T polymorphism might be associated with decreased risk for preeclampsia, but the 834+7G/A polymorphism is not associated with the disorder, in the Chinese population.

Background: Amnestic mild cognitive impairment (aMCI) is a syndrome characterized by significant forgetfulness that does not meet the criteria of dementia. Individuals with aMCI are at a bigger risk of progressing to dementia. Current studies suggest good sleep quality is linked with preserved cognition in the elderly, and sleep complaints are common among the elderly with amnesia. Therefore, improving their sleep may be helpful for maintaining and improving their cognitive capacity. According to the theory of traditional Chinese medicine, Yi-Zhi-An-Shen is an herbal compound which may ameliorate forgetfulness and sleep disorders. As growing evidence indicates that gut microbiome is associated with major mental symptoms, a hypothesis was proposed that Yi-Zhi-An-Shen Granules (YZASG) might work by alternating microbial abundance and diversity. In this study, the investigators intend to assess the efficacy of YZASG on global cognition in the elderly suffering from aMCI, and evaluate its safety as well as its potential mechanisms via sleep quality, fecal microbial 16SrDNA and metagenomics analyses, and serum markers. Methods: This is a randomized, double-blind, placebo-controlled clinical trial. A total of 80 patients (aged 60~85 years) will be recruited and allocated randomly to a treatment group and a placebo-matched group in a 1:1 ratio, then will be administered YZASG or isodose placebo three times a day. The intervention course is 16 weeks, with an 18-month follow-up. The primary outcome is Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-cog11). Secondary outcome measures are mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), Pittsburgh Sleep Quality Index (PSQI), serum concentrations of immunological factors and inflammatory cytokines, fecal microbiota. Fecal microbiota will only be collected at the baseline and endpoint of the intervention. Discussion: The results of this trial will be conducive to assessing the safety and effectiveness on cognition of YZASG in intervening aMCI among the elderly and determining if it takes effect via the improvement of sleep quality, regulation of gut microbita, concentration of certain serum markers. Trial Registration: ClinicalTrials.gov, ID: NCT03601000. Registered on 26 July 2018. Keywords: Amnestic Mild cognitive impairment (aMCI), Sleep, Gut microbiome, Older adults

Context and objective Preeclampsia is a pregnancy-specific disorder associated with oxidative stress. The glutathione S-transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1) have previously been reported. The aim of this study was to investigate the association of GST gene polymorphisms with the risk of preeclampsia in Chinese subjects. Study design The case-control population consists of 525 subjects. The genotyping of the GSTT1 and GSTM1 polymorphisms was carried out on genomic DNA using the multiplex polymerase chain reaction (PCR). We calculated odds ratios (ORs), adjusted for the confounding variables, to estimate the association between gene polymorphisms and preeclampsia. Results The GSTT1 null genotype was found to be protective from the development of preeclampsia (odds ratios 0.645, 95% confidence interval 0.421–0.989; P = 0.044). Further analysis showed that a combination of deletion genotypes of the GSTT1 and GSTM1 genes conferred an even lower risk of preeclampsia (OR = 0.470, 95%CI = 0.255-0.866; P = 0.015). There is no relationship between the GSTT1 and GSTM1 gene polymorphisms and blood pressure levels in pregnant women with and without preeclampsia. Conclusion Our data suggest that a GSTT1 null polymorphism might be associated with decreased risk for preeclampsia in the Chinese population, and that this risk decreases with the combination of both GSTT1 and GSTM1 null polymorphisms.

To investigate the relationship between polymorphisms of the growth arrest specific 6 (GAS6) gene and severe preeclampsia in a South West Han Chinese population.Blood samples from 167 patients with severe preeclampsia and 312 normal pregnant women as controls from Han Chinese in Chengdu area were analyzed by polymerase chain reaction-restriction fragment length polymorphisms.C and T allele frequencies for +1332C/T site were 85.63% and 14.37% in the patient group, respectively, and 78.04% and 21.96% in control group, respectively. The TT genotype and variant T allelic frequencies of the +1332C/T polymorphism were significantly lower in patients with severe preeclampsia than in the control group (both P0.05), and the odds ratio for the risk of severe preeclampsia was 0.602 (95%CI: 0.401-0.904) in carriers for the variant T allele (χThe variant GAS6+1332 T allele is associated with a decreased risk for severe preeclampsia in a South West Han Chinese population. On the other hand, the 834+7G/A polymorphism has no effect on the severe preeclampsia.

The investigation of novel genes involved in the derangement of glucose and lipid metabolism is of particular importance in understanding the development of metabolic syndrome (MS). In the present study, bioinformatic analyses were carried out to explore the structures and roles of the proteins encoded by the four cDNA sequences identified in our previous studies as associated with MS. Homology analyses demonstrated that the proteins encoded by Sequence 1, Sequence 2, Sequence 3, and Sequence 4 were homologous with fibrinogen gamma polypeptide, liver fibrinogen-like 1, chromosome 10 open reading frame 104, and an unnamed protein product, respectively. Because the structures were well-known for fibrinogen gamma polypeptide and liver fibrinogen-like 1, further analyses were performed only for Sequence 3 and Sequence 4. Analyses of functional domains showed that the predicted proteins encoded by Sequence 3 and Sequence 4 had multiple phosphorylation and myristoylation sites. These results indicated that the two predicted proteins might be intermediate proteins in some signaling pathways. In order to explore the possible association of Sequence 3 with MS, HepG2 cells, a human hepatoma cell line, were treated with different concentrations of glucose (mannitol as osmotic control) for 48 h. Glucose at concentrations of 22 and 33.3 mM significantly increased the mRNA expression of Sequence 3 compared to glucose at 5.6 mM while mannitol had no significant effect on the mRNA expression of Sequence 3. These results indicated that the mRNA expression of Sequence 3 was positively associated with glucose higher than physiological concentrations.