Crucial Roles of 5-HT and 5-HT2 Receptor in Diabetes-Related Lipid Accumulation and Pro-Inflammatory Cytokine Generation in Hepatocytes

Background/Aims: Previously, we confirmed that liver-synthesized 5-HT rather than non-liver 5-HT, acting on the 5-HT2 receptor (5-HT2R), modulates lipid-induced excessive lipid synthesis (ELS). Here, we further revealed the effects of the hepatocellular 5-HT system in diabetes-related disorders. Methods: Studies were conducted in male ICR mice, human HepG2 cells, and primary mouse hepatocytes (PMHs) under gene or chemical inhibition of the 5-HT system, key lipid metabolism, and inflammation-related factors. Protein and messenger RNA expression and levels of the factors were determined via western blotting, reverse transcription PCR, and quantitative assay kits, respectively. Hepatic steatosis with inflammation and fibrosis, intracellular lipid droplet accumulation (LDA), and reactive oxygen species (ROS) location were determined via hematoxylin and eosin, Masson’s trichrome, Oil red O, and fluorescent-specific staining, respectively. Results: Palmitic acid induced the activation of the 5-HT system: the activation of 5-HT2R, primarily 5-HT2AR, in addition to upregulating monoamine oxidase A (MAO-A) expression and 5-HT synthesis, by activating the G protein/ phospholipase C pathway modulated PKCε activation, resulting in ELS with LDA; the activation of NF-κB, which mediates the generation of pro-inflammatory cytokines, was primarily due to ROS generation in the mitochondria induced by MAO-A–catalyzed 5-HT degradation, and secondarily due to the activation of PKCε. These effects of the 5-HT system were also detected in palmitic acid- or high glucose-treated PMHs and regulated multiple inflammatory signaling pathways. In diabetic mice, co-treatment with antagonists of both 5-HT synthesis and 5-HT2R significantly abolished hepatic steatosis, inflammation, and fibrosis as well as hyperglycemia and dyslipidemia. Conclusion: Activation of the hepatocellular 5-HT system plays a crucial role in inducing diabetes-related hepatic dysfunction and is a potential therapeutic target

Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells.</p> <p>Methods</p> <p>Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The <it>in vitro </it>invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells.</p> <p>Results</p> <p>Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the <it>in vitro </it>invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the <it>in vitro </it>angiogenesis of cancer cells in a dose-dependent manner.</p> <p>Conclusions</p> <p>These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells <it>in vitro</it>, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer.</p

N‐P utilization of Acer mono leaves at different life history stages across altitudinal gradients

Abstract The relationship between plants and the environment is a core area of research in ecology. Owing to differences in plant sensitivity to the environment at different life history stages, the adaptive strategies of plants are a cumulative result of both their life history and environment. Previous research on plant adaptation strategies has focused on adult plants, neglecting saplings or seedlings, which are more sensitive to the environment and largely affect the growth strategy of subsequent life stages. We compared leaf N and P stoichiometric traits of the seedlings, saplings, and adult trees of Acer mono Maxim and different altitudes and found significant linear trends for both life history stages and altitude. Leaf N and P content by unit mass were greatly affected by environmental change, and the leaf N and P content by unit area varied greatly by life history stage. Acer mono leaf N‐P utilization showed a significant allometric growth trend in all life history stages and at low altitudes. The adult stage had higher N‐use efficiency than the seedling stage and exhibited an isometric growth trend at high altitudes. The N‐P utilization strategies of A. mono leaves are affected by changing environmental conditions, but their response is further dependent upon the life history stage of the plant. Thus, this study provides novel insights into the nutrient use strategies of A. mono and how they respond to the environmental temperature, soil moisture content along altitude and how these changes differ among different life history stages, which further provide the scientific basis for the study of plant nutrient utilization strategy on regional scale

Leaf Caloric Value from Tropical to Cold-Temperate Forests: Latitudinal Patterns and Linkage to Productivity.

Leaf caloric value (LCV) reflects the capacity of a leaf to fix and accumulate solar energy through photosynthesis. We systematically investigated the LCV of 745 plant species in 9 forests, representing a range of tropical to cold-temperate forests along the 4700-km North-South Transect of Eastern China. The goals were to explore the latitudinal patterns of LCV at the levels of species, plant functional group, and community and to establish the relationship between LCV and gross primary productivity (GPP). Our results showed that LCV for all species ranged from 12.85 to 22.15 KJ g-1 with an average of 18.46 KJ g-1. Plant functional groups had a significant influence on LCV, with trees > shrubs > herbs, conifers > broadleaved trees, and evergreens > deciduous trees. The different values of LCV represented the long-term evolution and adaptation of plant species to different environments. Unexpectedly, no apparent latitudinal trends of LCV at community level were observed, although LCV at the species level clearly decreased with increasing latitude. Use efficiency of LCV (CUE, gC KJ-1), defined as the ratio of GPP to total LCV at the community level, varied quadratic with latitude and was lower in the middle latitudes. Climate (temperature and precipitation) may explain 52.9% of the variation in spatial patterns of CUE, which was positively correlated with aridity. Our findings are the first large-scale report of the latitudinal patterns of LCV in forests at the species, plant functional group, and community levels and provide new insights into the relationship between LCV and ecosystem functions in forest communities

Antioxidant Properties of a Traditional Vine Tea, Ampelopsis grossedentata

Ampelopsis grossedentata, also called vine tea, has been used as a traditional beverage in China for centuries. Vine tea contains rich polyphenols and shows benefit to human health, but the chemical and antioxidant properties of vine tea polyphenols from different locations remain unclear. This study aims to investigate the chemical and antioxidant properties of vine tea from three major production areas in China including Guizhou, Hunan, and Guangxi Provinces. The highest amount of polyphenol from vine tea was extracted by 70% ethanol at 70 &deg;C for 40 min with ultrasonic treatment. The major compound in vine tea polyphenols (VTP) was determined as dihydromyricetin (DMY) by high-performance liquid chromatography (HPLC) and the content was estimated as 21.42%, 20.17%, and 16.47% of dry weight basis from Hunan, Guizhou, and Guangxi products, respectively. The antioxidant activities were investigated in vitro and in culture hepatic cells. VTP and DMY showed strong 1,1-Diphenyl-2-picrylhydrazyl free radical (DPPH) scavenging ability and high oxygen radical absorption capacity (ORAC) value in vitro. VTP and DMY also increased the level of nicotinamide adenine dinucleotide phosphate (NADPH):quinone oxidoreductase (NQO1) in HepG2 cells. Moreover, VTP and DMY enhanced the level of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced the level of Kelch-like ECH-associated protein 1 (Keap1). Taken together, our data demonstrated that the extraction of vine tea by 70% ethanol with ultrasonic treatment is a novel method to efficiently obtain components possessing stronger antioxidant activity. Furthermore, the results from the culture cells suggest that the bioactive component of vine tea might exert the antioxidant activity by activating the cellular Nrf2/Keap1 pathway

Regional response of grassland productivity to changing environment conditions influenced by limiting factors.

Regional differences and regulatory mechanisms of vegetation productivity response to changing environmental conditions constitute a core issue in macroecological researches. To verify the main limiting factors of different macrosystems [temperature-limited Tibetan Plateau (TP), precipitation-limited Mongolian Plateau (MP), and nutrient-limited Loess Plateau (LP)], we conducted a comparative survey of the east-west grassland transects on the three plateaus and explored the factors limiting regional productivity and their underlying mechanisms. The results showed that aboveground net primary productivity (ANPP) of LP (109.10 ± 16.76 g m-2 yr-1) was significantly higher than that of MP (66.71 ± 11.11 g m-2 yr-1) and TP (57.02 ± 10.59 g m-2 yr-1). The response rate of ANPP with environmental changes was different among different plateaus, being closely related to the main limiting factors. On MP, this was precipitation, on LP it was temperature and nutrients, and on TP, it was non-specific, reflecting restriction by the extremely low temperature. After autocorrelation screening of environmental factors, different regions exhibited different productivity response mechanisms. MP was mainly influenced by temperature and precipitation, LP was influenced by temperature and nutrient, and TP was influenced by nutrient, reflecting the modifying effect of the main limiting factors. The effect of each regional environment on ANPP was 72.56% on average and only 27.18% after simple regional integration. The regional model could optimize the simulation error of the integrated model, and the relative deviations in MP, LP, and TP were reduced by 31.76%, 17.22%, and 2.23%, respectively. These findings indicate that the grasslands on the three plateaus may have different or even the opposite mechanisms to control productivity

Description of the study sites.

<p>Description of the study sites.</p

Changes in leaf caloric value among different types of trees in Chinese forests.

<p>Panel A, C and B, D were calculated at each site and for the total transect, respectively. Data are represented as mean ± S.E. Different letters indicate a significant difference among plant functional types (<i>p</i> < 0.05).</p