No abstract

Constitutive activation of the nuclear factor-κB (NF-κB) transcription factor plays a key role in chronic colonic inflammation and colon tumorigenesis. However, the mechanisms by which the tightly regulated NF-κB pathway becomes constitutively activated during colonic pathogenesis remain obscure. Here, we report that PDLIM2, an essential terminator of NF-κB activation, is repressed in various human colorectal cancer cell lines, suggesting one important mechanism for the constitutive activation of NF-κB. Indeed, expression of exogenous PDLIM2 inhibited constitutive NF-κB activation in these colorectal cancer cells. Importantly, the PDLIM2 expression was sufficient to suppress in vitro anchorage-independent growth and in vivo tumor formation of these malignant cells. We have further shown that the PDLIM2 repression involves promoter methylation. Accordingly, treatment of the colorectal tumor cell lines with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine restored PDLIM2 expression and resulted in growth arrest. These studies thus provide new mechanistic insights into colon tumorigenesis by identifying a novel tumor suppressor role for PDLIM2. Cancer Res; 70(5); 1766-72. ©2010 AACR.

Increasing atmospheric nitrogen (N) deposition has the potential to alter plant diversity and thus the function and stability of terrestrial ecosystems. N-limited alpine ecosystems are expected to be particularly susceptible to increasing N deposition. However, little is known about the critical loads and saturation thresholds of ecosystem responses to increasing N deposition on the Tibetan Plateau, despite its importance to ecosystem management. To evaluate the N critical loads and N saturation thresholds in an alpine ecosystem, in 2010, we treated an alpine meadow with five levels of N addition (0, 10, 20, 40, and 80 kg N ha -1 year -1 ) and characterized plant and soil responses. The results showed that plant species richness and diversity index did not statistically vary with N addition treatments, but they both changed with years. N addition affected plant cover and aboveground productivity, especially for grasses, and soil chemical features. The N critical loads and saturation thresholds, in terms of plant cover and biomass change at the community level, were 8.8-12.7 and 50 kg N ha -1 -year -1 (including the ambient N deposition rate), respectively. However, pronounced changes in soil inorganic N and net N mineralization occurred under the 20 and 40 kg N ha -1 year -1 treatments. Our results indicate that plant community cover and biomass are more sensitive than soil to increasing N inputs. The plant community composition in alpine ecosystems on the Qinghai-Tibetan Plateau may change under increasing N deposition in the future.

No abstract

15-Hydroxyeicosatetraenoic acid (15-HETE), a product of arachidonic acid (AA) catalyzed by 15-lipoxygenase (15-LO), plays an essential role in hypoxic pulmonary arterial hypertension. We have previously shown that 15-HETE inhibits apoptosis in pulmonary artery smooth muscle cells (PASMCs). To test the hypothesis that such an effect is attributable to the hypoxia-induced pulmonary vascular remodeling (PVR), we performed these studies. We found subtle thickening of proximal media/adventitia of the pulmonary arteries (PA) in rats that had been exposed to hypoxia. This was associated with an up-regulation of the anti-apoptotic Bcl-2 expression and down-regulation of pro-apoptotic caspase-3 and Bax expression in PA homogenates. Nordihydroguaiaretic acid (NDGA), which inhibits the generation of endogenous 15-HETE, reversed all the alterations following hypoxia. In situ hybridization histochemistry and immunocytochemistry showed that the 15-LO-1 mRNA and protein were localized in pulmonary artery endothelial cells (PAECs), while the 15-LO-2 mRNA and protein were localized in both PAECs and PASMCs. Furthermore, the Rho-kinase (ROCK) pathway was activated by both endogenous and exogenous 15-HETE, alleviating the serum deprivation (SD)-induced PASMC apoptosis. Thus, these findings indicate that 15-HETE protects PASMC from apoptosis, contributing to pulmonary vascular medial thickening, and the effect is, at least in part, mediated via the ROCK pathway.

Increasing evidence indicates that mRNAs are often subject to posttranscriptional modifications. Among them, N6-methyladenosine (m6A), which has been shown to play key roles in RNA splicing, stability, nuclear export, and translation, is the most abundant modification of RNA. Extensive studies of m6A modification of mRNAs have been carried out, while little is known about m6A modification of long non-coding RNAs (lncRNAs). Recently, several studies reported m6A modification of lncRNAs. In this review, we focus on these m6A-modified lncRNAs and discuss possible functions of m6A modification.

Metabolic associated fatty liver disease (MAFLD) is recognized as the liver disease component of metabolic syndrome, which is mainly related to insulin resistance and genetic susceptibility. It is the most prevalent chronic liver disease worldwide. With rapid lifestyle transitions, its prevalence worldwide is increasing, and tremendous challenges in controlling this pandemic are arising. The objective of this study was to investigate the prevalence and risk factors of MAFLD in rural areas of Xinxiang, Henan in 2017. We conducted a cross-sectional analysis of rural inhabitants aged 20–79 years in Xinxiang, Henan in 2017, using cluster random sampling (N = 9140). Physical examinations were conducted at local clinics from April to June 2017. After overnight fasting, all participants underwent physical examinations, blood routine tests, biochemical examinations, and liver ultrasound and completed questionnaires. We investigated the crude and age-adjusted MAFLD prevalence and analyzed the characteristics of those with, and without, MAFLD, using logistic regression. Approximately 2868 (31.38%) participants were diagnosed with MAFLD. The overall age-adjusted MAFLD prevalence was 29.85% (men: 35.36%; women: 26.49%). The MAFLD prevalence increased with age, and peaked at the 50–59-year age group, and then began to decline. Higher body mass index, waist circumference, percentage of lymphocytes, levels of hemoglobin, platelet count, triglyceride, fasting plasma glucose, and serum uric acid were independently and positively correlated with MAFLD; In contrary, active physical activity and high-density lipoprotein cholesterol were negatively correlated with MAFLD. In summary, the MAFLD prevalence in the study population was 29.85%. Higher body mass index, waist circumference, percentage of lymphocytes, levels of hemoglobin, platelet count, triglyceride, fasting plasma glucose, and serum uric acid were risk factors for MAFLD.

The mechanisms underlying nutrient-induced diversity–stability relationships have been examined extensively. However, the effects of nutrient-induced shifts of dominant species on ecosystem stability have rarely been evaluated. We compiled a dataset from a long-term nitrogen (N) and phosphorus (P) enrichment experiment conducted in an alpine grassland on the Tibetan Plateau to test the effects of nutrient-induced shifts of dominant species on stability. Our results show that N enrichment increased synchrony among the dominant species, which contributed to a significant increase in synchrony of the whole community. Meanwhile, N-induced shifts in dominant species composition significantly increased population variability. Increases in species synchrony and population variability resulted in a decline in ecosystem stability. Our study has important implications for progress in understanding the role of plant functional compensation in the stability of ecosystem functions, which is critical for better understanding the mechanisms driving both community assembly and ecosystem functions.