EGTA, a calcium chelator, affects cell cycle and increases DNA methylation in root tips of Triticum aestivum L.

In this study, when germinated Triticum aestivum L. seeds were treated with 0, 2, 4 and 6 mM ethyl glycol tetraacetic acid (EGTA), root growth was suppressed and the mitotic index decreased. These inhibitory effects were positively correlated with EGTA concentration. RT-PCR analysis revealed that the expression of several gene markers related to the G1/S transition of the cell cycle were significantly downregulated. Confocal microscopy of Fluo-3/AM-stained roots showed chelation of nearly all of the Ca2+ within the root meristematic regions. Both random amplified polymorphic DNA (RAPD) and coupled restriction enzyme digestion-random amplification (CRED-RA) techniques showed significant increases in the levels of genomic DNA polymorphisms and degree of DNA methylation. The study provides information concerning the impact of Ca2+ chelator, EGTA, on the growth, expression of cell cycle transition marker genes, and changes in DNA structure and methylation in the wheat roots

Diurnal Variations in Neural Activity of Healthy Human Brain Decoded with Resting-State Blood Oxygen Level Dependent fMRI

It remains an ongoing investigation about how the neural activity alters with the diurnal rhythms in human brain. Resting-state functional magnetic resonance imaging (RS-fMRI) reflects spontaneous activities and/or the endogenous neurophysiological process of the human brain. In the present study, we applied the ReHo (regional homogeneity) and ALFF (amplitude of low frequency fluctuation) based on RS-fMRI to explore the regional differences in the spontaneous cerebral activities throughout the entire brain between the morning and evening sessions within a 24-h time cycle. Wide spread brain areas were found to exhibit diurnal variations, which may be attributed to the internal molecular systems regulated by clock genes, and the environmental factors including light-dark cycle, daily activities and homeostatic sleep drive. Notably, the diurnal variation of default mode network (DMN) suggests that there is an adaptation or compensation response within the subregions of DMN, implying a balance or a decoupling of regulation between these regions.National Natural Science Foundation of China [81371359]; National Basic Research Program of China [2015CB755500]; Basic Research Program of Shenzhen [JCYJ20160429191938883]SCI(E)[email protected]

Early-onset pancreatic neuroendocrine neoplasms: A distinct disease with improved survival compared with old individuals

BackgroundThe incidence, clinicopathologic characteristics, treatment patterns, and survival of early-onset pancreatic neuroendocrine neoplasms (EOPanNENs) have not been well explored.MethodsPatients diagnosed with PanNENs were identified from the SEER database between 2000 and 2018. EOPanNENs were defined as diagnosis in patients aged less than 50 years, while the remaining were defined as later-onset pancreatic neuroendocrine neoplasms (LOPanNENs). Incidence, clinical features, management, and prognosis were analyzed in our study. Multivariable analyses were performed to identify factors associated with overall survival (OS) in EOPanNENs and LOPanNENs, respectively.ResultsA total of 5172 patients with PanNENs were included: 1267 (24.5%) in the EOPanNENs cohort and 3905 (75.5%) in the LOPanNENs cohort. The age-adjusted incidence rate significantly increased among later-onset cases, while it remained relatively stable in early-onset cases. EOPanNENs were more frequently to be female, unmarried, and with better tumor differentiation compared with LOPanNENs. Of note, early-onset patients presented with a higher rate of lymph node involvement, and they were more likely to receive surgical treatment. For local-regional disease at presentation, surgery alone was the most frequently used regimen over the last two decades. With regard to distant stage, a combination of surgery and chemotherapy was more often utilized. Risk factors for PanNENs survival were more correlated with LOPanNENs compared with EOPanNENs. The OS and cancer-specific survival (CSS) were significantly better in the EOPanNENs group. Further analyses showed that EOPanNENs ≤ 2cm were associated with more favorable survival outcomes than EOPanNENs>2cm.ConclusionEOPanNENs are a clinically rare and distinct entity from LOPanNENs. The advantages in survival for the EOPanNENs cohort over time were largely driven by the indolent clinical courses including better tumor differentiation and intensified surgical treatment. Further investigations are warranted to better understand the characteristics of this disease subgroup

Hawthorn Procyanidins Regulate Lipid Metabolism through the AMPK/SREBP-1c Signaling Pathway

Objective: To investigate the effect of hawthorn procyanidins (HPC) on lipid metabolism and its mechanism by regulating the AMP-activated protein kinase/sterol regulatory element binding protein-1c (AMPK/SREBP-1c) signaling pathway. Methods: Sixty rats were randomly divided into six groups (n = 10) blank control (BC), hyperlipidemia model (HM), low-, medium-, and high-dose HPC (HPC-LD, HPC-MD, and HPC-HD) and fenofibrate positive control (FP). The contents of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the serum and liver homogenate were measured by commercial kits. Hematoxylin eosin (HE) staining was used to observe hepatic histopathological changes. The mRNA expression levels of AMPK, SREBP-1c, glycerol-3-phosphate acyltransferase-1 (GPAT1), acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), carnitine palmitoyltransterase-1 (CPT1) and peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) in the liver were measured by quantitative real-time polymerase chain reaction (PCR). Western blotting was used to detect the protein expression of p-AMPK, SREBP-1c, GPAT1, ACC, FAS, CPT1 and PGC-1α in the liver. Results: After seven weeks of feeding on a high-fat diet, body mass, liver mass and liver index significantly increased compared with the control group fed on a basal diet (P < 0.05 or < 0.01). Compared with the HM group, the contents of TG, TC and LDL-C in serum and liver homogenate in the HPC-HD and FP groups significantly decreased, and the content of HDL-C significantly increased (P < 0.01); the effect of HPC on lipid content in serum and liver homogenate was dose-dependent. After prophylactic intervention with HPC, the steatosis of hepatocytes was gradually improved with an increase in the dosage of HPC. Compared with the HM group, the AMPK mRNA expression and p-AMPK protein expression in liver tissues in the HPC-HD and FP groups significantly increased (P < 0.01), and the mRNA and protein expression of SREBP-1c, GPAT1, ACC and FAS significantly decreased (P < 0.01), and the mRNA and protein expression of CPT1 and PGC-1α significantly increased in the liver (P < 0.01). Conclusion: HPC can effectively improve lipid metabolism in hyperlipidemic rats, which may be related to the regulation of the AMPK/SREBP-1c signaling pathway

Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen

<p>Abstract</p> <p>Background</p> <p>Synuclein gamma (SNCG), initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA) levels.</p> <p>Methods</p> <p>SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS.</p> <p>Results</p> <p>SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS) and overall survival (OS) (<it>P </it>< 0.0001). Multivariate analysis revealed that both tissue SNCG and serum CEA were independent prognostic factors of DFS (<it>P </it>= 0.001, <0.0001, respectively) for 170 patients with colon adenocarcinomas. Importantly, SNCG remained a prognostic determinant of DFS and OS (<it>P </it>= 0.001, 0.002) for 97 patients with normal preoperative serum CEA level.</p> <p>Conclusions</p> <p>Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.</p