Melamine induced changes in histopathology of the main organs and transcriptional levels of MAPK signaling genes in kidneys of female mice.

Melamine is an important chemical raw material used in industries, which has potential health risks to animals and humans. Current research mainly focuses on the toxic effects of high-dose melamine ingestion. However, there are few reports on whether melamine at the current limited standard dose has adverse effects on various tissues and organs, and whether there are sensitive target genes for risk evaluation. For this, 24 female Kunming mice were fed 0, 1.8-, 3.6-, and 7.2- mg/kg/d melamine via drinking water for consecutive 28 days, respectively. The morphological changes of the ovarian, hepatic, and renal tissues were firstly observed. The results demonstrated that the histopathology of ovary, liver, and especially in kidney had been altered by melamine intake in female. And then, the transcriptional levels of MAPK signaling genes including p38, ERK1, ERK2, JNK1, and JNK2 in kidneys were investigated by real-time PCR. The data showed that ERK1 and p38 mRNAs expressions were up-regulated significantly by melamine, suggesting that ERK1 and p38 transcriptional levels in the kidney might to be considered as candidate targets for lower-dose melamine toxicity. This study not only provides potential targets for the diagnosis and prevention of melamine damage, but also helps to assess the health risks of the current minimum allowable levels of melamine in food and environment.

Vitamin C affects G0/G1 cell cycle and autophagy by downregulating of cyclin D1 in gastric carcinoma cells.

Vitamin C has re-emerged as a promising anticancer agent. This study attempts to analyze the differential gene expression of profiles GSE11919 to look for some clues, and the most significant cell cycle pathway caused by vitamin C was identified by integrated bioinformatics analysis. Inspired by this, we investigated the effect of vitamin C treatment on gastric carcinoma cells by detection of cell cycle, apoptosis, and autophagy. Vitamin C significantly elevated the percentage of cells at G0/G1 phase, whereas the percentage of S phase cells was decreased. Meanwhile, vitamin C treatment resulted in downregulation of cell cycle-related protein Cyclin D1. We deduced that the downregulation of Cyclin D1 by vitamin C accompanied by significantly increased 5'AMP-activated protein kinase and induced autophagy in MKN45 cells. These results suggest that vitamin C has the antiproliferation effect on gastric carcinoma cells via the regulation of cell cycle and autophagy by Cyclin D1.

Arabidopsis COP1-interacting protein 1 is a positive regulator of ABA response.

COP1-interacting protein 1 (CIP1, At5g41790) was the first reported interacting protein for CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) of Arabidopsis; however its physiological function has remained unknown for two decades. Here we show that CIP1 is a positive regulator of abscisic acid (ABA) response. CIP1 is mainly expressed in the photosynthetic cells and the vascular tissue, and its promoter activity can be induced by osmotic stress and ABA. The CIP1 protein is localized to the plasma membrane. A T-DNA insertion mutant cip1-1 was then characterized. The mutant is sensitive to osmotic stress and has ABA insensitive phenotypes. RNA sequencing showed that cip1-1 has lower levels of gene expression in abiotic stress response compared with the wild-type. Meanwhile, transcript levels of ABA biosynthesis genes are higher in cip1-1 than in the wild-type. These results suggested that CIP1 is positively involved in ABA response.

[Bioinformatic analysis of molecular mechanism of IL-17 in regulating ulcerative colitis].

Objective To identify hub genes and key pathways in ulcerative colitis (UC) by bioinformatics. Methods The mRNA expression microarray GSE134025 related to ulcerative colitis was retrieved from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between ulcerative colitis samples and normal intestinal mucosal cells were screened by the R limma package, and then GO and KEGG pathway analysis was carried out. The protein-protein interaction (PPI) network was constructed by STRING database, and Cytoscape software was used to screen the hub genes in the PPI network. KEGG mapper was employed to mark the location of the hub genes in signal pathway. Results A total of 190 DEGs were screened, of which 147 were up-regulated and 43 were down-regulated. GO function enrichment showed hub genes were mainly involved in biological processes including inflammatory response and positive regulation of proliferation. Cellular component mainly enriched in membrane and plasma membrane, maintaining the molecular functions of mediating heparin binding and cytokines. KEGG analysis showed that the enriched pathways are mainly related to cytokine-cytokine receptor interaction, chemokine signaling pathway and other signal transduction pathway. Ten hub genes such as IL-6, CXCL8, CXCL10, CXCL1, CXCL9, ANXA1, IL-1ß, CCL20, CXCL2, and CXCL11 were screened out of the PPI network, which were located downstream of the signaling pathway regulated by IL-17. Conclusion The 10 hub genes related to the risk of UC were likely to be regulated by IL-17 during the occurrence and development of UC.

Gender-specific effects of oxidative balance score on the prevalence of diabetes in the US population from NHANES.

Background: The relationship between oxidative balance score (OBS) and diabetes remains poorly understood and may be gender-specific. We conducted a cross-sectional study to investigate the complex association between OBS and diabetes among US adults. Methods: Overall, 5,233 participants were included in this cross-sectional study. The exposure variable was OBS, composed of scores for 20 dietary and lifestyle factors. Multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were applied to examine the relationship between OBS and diabetes. Results: Compared to the lowest OBS quartile group (Q1), the multivariable-adjusted odds ratio (OR) (95% confidence interval (CI) for the highest OBS quartile group (Q4) was 0.602 (0.372-0.974) (p for trend = 0.007), and for the highest lifestyle, the OBS quartile group was 0.386 (0.223-0.667) (p for trend < 0.001). Moreover, gender effects were found between OBS and diabetes (p for interaction = 0.044). RCS showed an inverted-U relationship between OBS and diabetes in women (p for non-linear = 6e-04) and a linear relationship between OBS and diabetes in men. Conclusions: In summary, high OBS was negatively associated with diabetes risk in a gender-dependent manner.

Clonal Architectures Predict Clinical Outcome in Gastric Adenocarcinoma Based on Genomic Variation, Tumor Evolution, and Heterogeneity.

Stomach adenocarcinoma (STAD) is a highly heterogeneous disease. Due to the lack of effective molecular markers and personalized treatment, the prognosis of gastric cancer patients is still very poor. The ABSOLUTE algorithm and cancer cell fraction were used to evaluate the clonal and subclonal status of 349 TCGA (The Cancer Genome Cancer Atlas)-STAD patients. Non-negative matrix factorization was used to identify the mutation characteristics of the samples. Univariate Cox regression analysis was used to determine the relationship between clonal/subclonal events and prognosis, and the Spearman correlation was used to evaluate the relationship of clonal/subclonal events to tumor mutation burden (TMB) and neoantigens. The evolution pattern of STAD demonstrated great tumor heterogeneity. TP53, USH2A, and GLI3 appeared earliest in STAD and may drive STAD. CTNNB1, LRP1B, and ERBB4 appeared the latest in STAD, and may be related to STAD's progress. Univariate Cox regression analysis identified four early genes, eight intermediate genes, and seven late genes significantly associated with overall survival. The number of subclonal events in the T stage was significantly different. The N stage, gender, and histological type were significantly different for clonal events, and there was a significant correlation between clonal/subclonal events and TMB/neoantigens. Our results highlight the importance of systematic evaluation of evolutionary models in the clinical management of STAD and personalized gastric cancer treatment.

Functions of autophagy in plant carbon and nitrogen metabolism.

Carbon and nitrogen are essential components for plant growth. Although models of plant carbon and nitrogen metabolisms have long been established, certain gaps remain unfilled, such as how plants are able to maintain a flexible nocturnal starch turnover capacity over various light cycles, or how nitrogen remobilization is achieved during the reproductive growth stage. Recent advances in plant autophagy have shed light on such questions. Not only does autophagy contribute to starch degradation at night, but it participates in the degradation of chloroplast proteins and even chloroplasts after prolonged carbon starvation, thus help maintain the free amino acid pool and provide substrate for respiration. The induction of autophagy under these conditions may involve transcriptional regulation. Large-scale transcriptome analyses revealed that ATG8e belongs to a core carbon signaling response shared by Arabidopsis accessions, and the transcription of Arabidopsis ATG7 is tightly co-regulated with genes functioning in chlorophyll degradation and leaf senescence. In the reproductive phase, autophagy is essential for bulk degradation of leaf proteins, thus contributes to nitrogen use efficiency (NUE) both under normal and low-nitrogen conditions.