Preterm delivery and sub-optimal fetal growth are associated with each other and affect both mother and infant. Our aim was to determine (i) whether there are detectable differences in DNA methylation between early and late gestation and (ii) whether changes in DNA methylation from entry are associated with spontaneous preterm delivery with and without reduced fetal growth.We conducted a case-control study nested within a large prospective cohort. Gene specific methylation was measured by Methyl-Profiler PCR Array in a Human Breast Cancer Signature Panel of 24 genes from maternal peripheral leukocytes genomic DNA at entry and 3rd trimester (sampled at 16 and 30 weeks of gestation, respectively). Clonal bisulfite DNA sequencing was performed to confirm the changes in selected genes (CYP1B1, GADD45A and CXCL12). Multivariable analysis was used for data analysis.There was significantly decrease in DNA methylation in 15 of 24 genes during the 3rd trimester in cases of spontaneous preterm delivery (n=23) as compared to the controls (n=19) (p<0.05-p<0.01 for each gene). Similar results were observed by bisulfite sequencing for 3 genes. The change in DNA methylation between late and early gestation was significantly different in cases (overall decrease in methylation was -4.0 ± 1.5%) compared to the controls (overall increase in methylation was 12.6 ± 2.19%, p<0.0001). A graded pattern of DNA methylation was observed in 15 genes. Cases who delivered preterm with reduced fetal growth had the lowest level of methylation, cases delivering preterm without reduced fetal growth were next and term controls were highest in methylation (p for trend <0.05 to p<0.01 for each gene). Cases of preterm delivery also had significantly lower dietary choline intake.These data suggest that epigenetic modification is associated with an increased risk of spontaneous preterm delivery, spontaneous preterm delivery with reduced fetal growth in particular.
Abstract A rat pheochromocytoma cell line (PC12 cells) was used as a model to investigate the role of calmodulin and its multiple mRNAs in NGF‐induced neuronal differentiation. The effect of NGF on the degree of differentiation was assayed using a simple differentiation scoring system. Significant increases in the differentiation score were seen by one day, and the scores increased about 10‐fold by 8 days of treatment. NGF also increased calmodulin in the PC12 cells; significant increases were seen by 2 days of treatment, and a maximum increase of 3‐fold was seen by 4 days. Northern blot analysis using a calmodulin riboprobe revealed that all five calmodulin mRNAs found in rat tissue were present in PC12 cells. The relative abundance of the calmodulin mRNAs was 1.7 ≥ 1.4 ≥ 2.3 ≥ 4.1 ≥ 0.9 kb. NGF treatment caused a differential increase in these mRNAs. The 1.4 kb transcript (from Gene II) was increased earlier (at 1 day) and to a greater extent (3‐fold) than any of the other mRNAs. Studies of the half‐lives (t 1/2 ) of these mRNAs suggested that the t1/2 varied with the mRNA; the smaller the mRNA, the shorter the t1/2. However, there were no significant effects of NGF on the t1/2 of any of the mRNAs. These studies indicate that NGF elevates calmodulin in PC12 cells by causing a differential increase in the multiple mRNAs for calmodulin and that the increase in calmodulin may play some part in NGF‐induced neuronal differentiation in PC12 cells.
BACKGROUND:The expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is increased in several human tumors, including colorectal carcinoma (CRC). The aim of this study was to compare the expression ALDH1A1 in CRC tumor tissue compared with non-tumor adjacent tissue (NAT), using immunohistochemistry (IHC), and to determine whether the expression of the ALDH1A1 protein was associated with prognostic factors in CRC. MATERIAL AND METHODS:Formalin-fixed paraffin-embedded (FFPE) tissue from 424 patients diagnosed with CRC, and 196 matched NATs were used to prepare tissue microarrays (TMAs). IHC was performed using an immunoperoxidase method with a primary polyclonal rabbit anti-ALDH1A1 antibody. The IHC scores by light microscopy were the staining intensity (scored from 0–3) multiplied by the percentage area of positive immunostaining within the visual field (scored from 0–4). Associations between tumor expression levels of ALDH1A1 and patient clinicopathological characteristics, including tumor grade, size, and TNM stage at surgery were analyzed. RESULTS:ALDH1A1 protein expression was significantly increased in CRC tissues compared with matched NATs. In patients with CRC, increased expression of the ALDH1A1 protein was significantly associated with the presence of lymph node metastasis: 64.28% in N0 cases; 75.49% in N1 cases; and 82.14% in N2 cases, (P=0.002). Univariate and multivariate analysis showed that ALDH1A1 expression was an independent prognostic marker for CRC (P<0.001). CONCLUSIONS:Using IHC, the expression of the ALDH1A1 protein in CRC tissues was significantly associated with the presence of lymph node metastases and might be a potential prognostic marker in patients with CRC.
In view of the great important role of literature database in automation of libraries, it clarifies that a small library must take standardized and specified procedure in the construction and maintenance of its database, for which an overall capacity building of the technicians constructing and maintaining the database is critical.
Objective To investigate the effect of keratinocyte growth factor(KGF) at different concentrations on the proliferation of pancreatic ductal epithelial cells(PDECs).Methods The PDECs were identified by immunocytochemical stain and RT-PCR.PDECs counting was carried out at different KGF concentrations.Results Nestin and CK19 were positively expressed in PDECs by RT-PCR and immunocytochemical stain;PDECs were stimulated by different concentrations of KGF after 2 days,and PDECs number stimulated by 20 μg/L KGF was 0.35±0.03,much higher than that of the control group which was 0.27±0.02.Conclusions KGF at different concentrations can significantly stimulate the proliferation of PDECs,the optimized concentration found in our tests is 20 μg/L.
Objective:To investigate the effects of Licorzinc Granules on Ulcer Healing and Expressions of EGF and EGFR in Gastric Ulcer Model in Rats.Methods:60 Wistar rats were randomly divided into six groups:normal group(n=10),model group(n=10),ranitidine group(n=10),licorzinc granules of high-dose group(n=10),licorzinc granules of mid-dose group(n=10),licorzinc granules of small-dose group(n=10)prepared by using icy acetic acid.Rats after 14days of continuous intragastric administration in the last administration after fasting for 24 hours,free drinking water,the first 16days will be broken cervical rats were sacrificed,drawing.Results were observed by HE staining,immunohistochemical staining and western blot.Results:①HE staining :Normal group:the rat gastric antral wall structural ntegrity,glandular mucosa neat,and there was no obvious inflammatory cell infiltration.Model group:Gastric telangiectasia,congestive,focal bleeding obvious that a large number of interstitial infiltration of inflammatory cells,and some regional mucosal necrosis,exfoliated,local glands damaged.Treatment group:ranitidine,Licorzinc Granules for high-dose and the dose of mucosal ulceration were observed varying degrees of healing ulcer lesions have varying degrees of the surface epithelium new coverage,inflammatory cells decreased significantly,we can see that the nascent gland hyperplasia coverage ulcers and fibrous connective tissue,obviously at the bottom of ulcer formation of granulation tissue,vascular mild gastric expansion,congestive.②Mmunohistochemical staining showed that EGF and EGFR expressions in normal group and model group were weak.EGF and EGFR expressions in licorzinc granules of high-dose group and of mid-dose group and the ranitidine group were significant intensive.EGF and EGFR expressions in licorzinc granules of small-dose group and model group were not obvious.③Western blot :The proportion between EGFR andβ-actin show that the expression of EGFR in licorzinc granules of high-dose group and mid-dose group and ranitidine group were significant intensive.In nomal group and model group and small-dose group were not obvious.Conclusion:Licorzinc granules can protect gastric tissue and accelerate ulcer healing by decreasing ulcer index of gastric ulcer rats model and increasing expressions of EGF and EGFR protein in the gastric tissue.
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