Inhibitor of growth 4 inhibits cell proliferation,migration, and induces apoptosis of renal cell carcinoma cells

The inhibitor of growth 4 (ING4) is known as a tumor suppressor. The expressions of ING4 were markedly reduced in human renal clear cell carcinoma (ccRCC) tissues. However, the role of ING4 in renal cell carcinoma (RCC) remains unknown. The aim of the current study was to detect the ING4 expression level and its potential role in human RCC cell lines. Our results showed that ING4 was lowly expressed in human RCC cell lines compared with that in proximal tubular cell line. Ectopic overexpression of ING4 inhibited the proliferation, migration, and invasion properties, and as well as prevented epithelial-mesenchymal transition (EMT) phenotype of RCC cells. In addition, ING4 overexpression induced cell apoptosis and autophagy in RCC cells. Furthermore, ING4 overexpression suppressed the activation of PI3K/Akt pathway in RCC cells. The activator of PI3K/Akt, insulin-like growth factor 1, abolished the effects of ING4 on RCC cells. These findings indicated that ING4 presented anticancer activity in RCC cells. The effects of ING4 on RCC cells were mediated by regulating the PI3K/Akt pathway. These findings suggested that ING4 could be used for gene therapy of RCC.     

EIF1A depletion restrains human pituitary adenoma progression

EIF1A encodes a translation initiation factor in eukaryocyte and aberrant expression of EIF1A is deemed to be associated with dysfunctions in intracranial diseases. The goal of this research was to explore the impacts of EIF1A on progression of human pituitary adenoma (PA). We employed immunohistochemistry to assess the expression of EIF1A in PA and para-carcinoma tissues. After constructing EIF1A-knockdown cell models via lentivirus infection, we examined cell proliferation through CCK-8 assay and Celigo cell counting assay. Flow cytometry was utilized to detect cell apoptosis and the migration ability of experimental cells was estimated using wound-healing assay and Transwell assay. The activity of the apoptosis-related factor, Caspase 3, was also examined via Caspase 3 activity assay. Lastly, in vivo xenograft mouse models were established to verify findings derived from in vitro cell models. Our results affirmed upregulation of EIF1A in PA cells and revealed that depletion of EIF1A could seriously limit cell proliferation and weaken the capacity of cell migration, and also enhance apoptosis of tumor cells. Mechanistically, degradation in cell growth mediated by EIF1A knockdown may involve in activation of MAPK signaling but inactivation of PI3K/AKT signaling pathway. This study indicates EIF1A plays a prominent role in facilitating tumor cell proliferation and migration which may further contribute to PA progression.Key words: EIF1A, Pituitary adenoma, Cell proliferation, Cell migration, MAPK     

Dopamine D3 receptor signaling alleviates mouse rheumatoid arthritis by promoting Toll-like receptor 4 degradation in mast cells

Dopamine receptors are involved in several immunological diseases. We previously found that dopamine D3 receptor (D3R) on mast cells showed a high correlation with disease activity in patients with rheumatoid arthritis, but the mechanism remains largely elusive. In this study, a murine collagen-induced arthritis (CIA) model was employed in both DBA/1 mice and D3R knockout mice. Here, we revealed that D3R-deficient mice developed more severe arthritis than wild-type mice. D3R suppressed mast cell activation in vivo and in vitro via a Toll-like receptor 4 (TLR4)-dependent pathway. Importantly, D3R promoted LC3 conversion to accelerate ubiquitin-labeled TLR4 degradation. Mechanistically, D3R inhibited mTOR and AKT phosphorylation while enhancing AMPK phosphorylation in activated mast cells, which was followed by autophagy-dependent protein degradation of TLR4. In total, we found that D3R on mast cells alleviated inflammation in mouse rheumatoid arthritis through the mTOR/AKT/AMPK-LC3-ubiquitin-TLR4 signaling axis. These findings identify a protective function of D3R against excessive inflammation in mast cells, expanding significant insight into the pathogenesis of rheumatoid arthritis and providing a possible target for future treatment.Subject terms: Immunological disorders, Rheumatic diseases     

Effect of Xanthan Gum on the Freeze-Thaw Stability of Wheat Gluten

Food Biophysics - The effect of xanthan gum on the freeze-thaw stability of wheat gluten was evaluated during a 60-day storage period at −18 °C with thawing every...     

鱼类基因内含子研究进展

内含子是指断裂基因中的非编码区序列,在编码蛋白质前被去除。在高等生物中,内含子的长度远大于外显子,大部分随机突变会发生在内含子中。因此,内含子的存在使高等生物对突变的耐受能力大大增强了。研究表明,内含子可以提高基因表达效率;影响RNA的转录、剪接加工、出核孔以及翻译等过程;启动某些基因的表达;并通过选择性剪接调控基因的表达。内含子功能的研究成果给当前鱼类免疫基因研究开拓了全新的视野。对内含子的分类、剪接、功能以及鱼类内含子研究的新进展进行了综述,并展望了内含子在鱼类免疫基因研究中的应用。     

Antagonistic and synergistic effects of bone morphogenetic protein 2/7 and all‐trans retinoic acid on the osteogenic differentiation of rat bone marrow stromal cells

The osteogenesis of bone marrow stromal cells (BMSCs) is of paramount importance for the repair of large‐size bone defects, which may be compromised by the dietary‐accumulated all‐trans retinoic acid (ATRA). We have shown that heterodimeric bone morphogenetic protein 2/7 (BMP2/7) could induce bone regeneration in a significantly higher dose‐efficiency in comparison with homodimeric BMPs. In this study, we evaluated the effects of ATRA and BMP2/7 on the proliferation, differentiation, mineralization and osteogenic genes. ATRA and BMP2/7 exhibited both antagonistic and synergistic effects on the osteogenesis of BMSCs. ATRA significantly inhibited proliferation and expression of osteocalcin but enhanced the activity of alkaline phosphatase of BMSCs. On day 21, 50 ng/mL BMP2/7 could antagonize the inhibitive effects of ATRA and significantly enhance osteogenesis of BMSCs. These findings suggested a promising application potential of heterodimeric BMP2/7 in clinic to promote bone regeneration for the cases with dietary accumulated ATRA.     

Stoichiometry and large-scale patterns of leaf carbon and nitrogen in the grassland biomes of China

Nitrogen (N) and carbon–nitrogen (C:N) ratio are key foliar traits with great ecological importance, but their patterns across biomes have only recently been explored. We conducted a systematic census of foliar C, N and C:N ratio for 213 species, from 41 families over 199 research sites across the grassland biomes of China following the same protocol, to explore how different environmental conditions and species composition affect leaf N and C:N stoichiometry. Leaf C:N stoichiometry is stable in three distinct climatic regions in Inner Mongolia, the Tibetan Plateau, and Xinjiang Autonomous Region, despite considerable variations among co-existing species and among different vegetation types. Our results also show that life form and genus identity explain more than 70% of total variations of foliar N and C:N ratio, while mean growing season temperature and growing season precipitation explained only less than 3%. This suggests that, at the biome scale, temperature affects leaf N mainly through a change in plant species composition rather than via temperature itself. When our data were pooled with a global dataset, the previously observed positive correlation between leaf N and mean annual temperature (MAT) at very low MATs, disappeared. Thus, our data do not support the previously proposed biogeochemical hypothesis that low temperature limitations on mineralization of organic matter and N availability in soils lead to low leaf N in cold environments.     

Role of AGEs in the progression and regression of atherosclerotic plaques

The formation of advanced glycation end-products(AGEs) is an important cause of metabolic memory in diabetic patients and a key factor in the formation of atherosclerosis(AS) plaques in patients with diabetes mellitus. Related studies showed that AGEs could disrupt hemodynamic steady-state and destroy vascular wall integrity through the endothelial barrier damage, foam cell(FC) formation, apoptosis, calcium deposition and other aspects. At the same time, AGEs could initiate oxidative stress and inflammatory response cascade via receptor-depended and non-receptor-dependent pathways, promoting plaques to develop from a steady state to a vulnerable state and eventually tend to rupture and thrombosis. Numerous studies have confirmed that these pathological processes mentioned above could lead to acute coronary heart disease(CHD) and other acute cardiovascular and cerebrovascular events. However, the specific role of AGEs in the progression and regression of AS plaques has not yet been fully elucidated. In this paper, the formation, source, metabolism, physical and chemical properties of AGEs and their role in the migration of FCs and plaque calcification are briefly described, we hope to provide new ideas for the researchers that struggling in this field.