LncRNA-HOTAIR promotes endothelial cell pyroptosis by regulating the miR-22/NLRP3 axis in hyperuricaemia

Long non-coding RNA (lncRNA) plays an important role in the renal inflammatory response caused by hyperuricaemia. However, the underlying molecular mechanisms through which lncRNA is involved in endothelial injury induced by hyperuricaemia remain unclear. In this study, we investigated the regulatory role of lncRNA-HOTAIR in high concentration of uric acid (HUA)–induced renal injury. We established hyperuricaemia mouse model and an in vitro uric acid (UA)–induced human umbilical vein endothelial cell (HUVEC) injury model. In HUA-treated HUVECs and hyperuricaemia mice, we observed increased HOTAIR and decreased miR-22 expression. The expression of pyroptosis-associated protein (NLRP3, Caspase-1, GSDMD-N, GSDMD-FL) was increased. The release of LDH, IL-1β and IL-18 in cell supernatants and the sera of model mice was also increased. The proliferation of HUVECs stimulated by HUA was significantly inhibited, and the number of TUNEL-positive cells in hyperuricaemia mouse kidney was increased. Bioinformatics analysis and luciferase reporter and RIP assays confirmed that HOTAIR promoted NLRP3 inflammasome activation by competitively binding miR-22. In gain- or loss-of-function experiments, we found that HOTAIR and NLRP3 overexpression or miR-22 knock down activated the NLRP3 inflammasome and promoted pyroptosis in HUA-treated HUVECs, while NLRP3 and HOTAIR knockdown or a miR-22 mimic exerted the opposite effects. Furthermore, in vivo experiments validated that HOTAIR knockdown alleviated renal inflammation in hyperuricaemia mice. In conclusion, we demonstrated that in hyperuricaemia, lncRNA-HOTAIR promotes endothelial cell pyroptosis by competitively binding miR-22 to regulate NLRP3 expression.     

Peptides YYGGEGSSSEQG and SESEM Inhibit TNF-α-Induced Smooth Muscle Cells Proliferation and Migration Through Their Bindings to TNF-α Receptor

International Journal of Peptide Research and Therapeutics - The peptides YYGGEGSSSEQG and SESEM derived from rice α-globulin have been reported to possess anti-atherosclerotic activity, but...     

Hydrogen sulphide reduces hyperhomocysteinaemia-induced endothelial ER stress by sulfhydrating protein disulphide isomerase to attenuate atherosclerosis

Hyperhomocysteinaemia (HHcy)-impaired endothelial dysfunction including endoplasmic reticulum (ER) stress plays a crucial role in atherogenesis. Hydrogen sulphide (H₂S), a metabolic production of Hcy and gasotransmitter, exhibits preventing cardiovascular damages induced by HHcy by reducing ER stress, but the underlying mechanism is unclear. Here, we made an atherosclerosis with HHcy mice model by ApoE knockout mice and feeding Pagien diet and drinking L-methionine water. H₂S donors NaHS and GYY4137 treatment lowered plaque area and ER stress in this model. Protein disulphide isomerase (PDI), a modulation protein folding key enzyme, was up-regulated in plaque and reduced by H₂S treatment. In cultured human aortic endothelial cells, Hcy dose and time dependently elevated PDI expression, but inhibited its activity, and which were rescued by H₂S. H₂S and its endogenous generation key enzyme-cystathionine γ lyase induced a new post-translational modification-sulfhydration of PDI. Sulfhydrated PDI enhanced its activity, and two cysteine-terminal CXXC domain of PDI was identified by site mutation. HHcy lowered PDI sulfhydration association ER stress, and H₂S rescued it but this effect was blocked by cysteine site mutation. Conclusively, we demonstrated that H₂S sulfhydrated PDI and enhanced its activity, reducing HHcy-induced endothelial ER stress to attenuate atherosclerosis development.     

New Phenylpropanoid Glycosides from Illicium majus and Their Radical Scavenging Activities

Chemical investigation of the ethanol extract of the branch and leaves of Illicium majus resulted in the isolation of four new phenylpropanoid glycosides ( 1 – 4 ) and one new phenolic glycoside ( 9 ), along with 13 known ones. Spectroscopic techniques were used to elucidate the structures of the new isolates such as 3-[(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydro-1-benzofuran-5-yl]propyl β-D-glucopyranoside ( 1 ), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-β-D-glucopyranoside ( 2 ), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-β-D-xylopyranoside ( 3 ), 3-[(2R,3S)-3-({[2-O-(4-O-acetyl-α-L-rhamnopyranosyl)-β-D-xylopyranosyl]oxy}methyl)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-2,3-dihydro-1-benzofuran-5-yl]propyl acetate ( 4 ), and 4-(2-hydroxyethyl)phenyl 3-O-β-D-glucopyranosyl-β-D-glucopyranoside ( 9 ). Free radical scavenging activities of the isolates were elucidated through the DPPH assay method. The most active compounds, 1-O-caffeoyl-β-D-glucopyranose ( 17 ) and soulieana acid 1 ( 18 ), exhibited moderate radical scavenging activities (IC₅₀=37.7±4.4 μM and IC₅₀=97.2±3.4 μM, respectively). The antibacterial activities of the isolates against Staphylococcus aureus and Escherichia coli were also assessed, and no activity was shown at the measured concentration (<32 μg/mL).     

非结构性碳水化合物与氮分配对美洲黑杨和青杨耐盐能力的影响

土壤盐渍化是阻碍林业发展的重要原因, 杨树(Populus spp.)是中国主要的人工林树种, 探究盐胁迫下植物的碳氮代谢特征与抗盐胁迫能力, 将有助于杨树人工林的可持续发展。该研究利用美洲黑杨(P. deltoides)和青杨(P. cathayana)两个物种, 采用去叶与不去叶处理, 在盐胁迫下研究两种杨树的抗逆性差异。研究发现, 盐胁迫下美洲黑杨的总生物量和光合能力均显著高于青杨。盐胁迫与去叶处理导致美洲黑杨叶绿素浓度和光系统II最大光量子效率显著高于青杨, 表明去叶对美洲黑杨影响较小, 但是加重了盐对青杨的毒害作用。美洲黑杨茎叶Na⁺浓度显著低于青杨, 表明美洲黑杨能够有效地限制Na⁺向地上部分运输。在盐胁迫条件下, 美洲黑杨茎和根比青杨能够维持更高浓度的淀粉、可溶性糖以及蔗糖, 前者较高的腺苷二磷酸葡萄糖焦磷酸化酶活性促进了光合产物向淀粉转换, 保证植物有充足的非结构性碳水化合物来参与渗透调节和维持其他生命活动, 而去叶使得青杨非结构性碳水化合物严重不足, 受盐胁迫影响更严重。盐胁迫下, 青杨分布在脂溶性蛋白(膜系统相关蛋白质)的氮浓度显著下降, 而NH₄⁺、谷氨酸脱氢酶活性与脯氨酸浓度显著升高。研究结果证明, 非结构性碳水化合物的积累、转化和分配是植物抗逆性的重要特征。     

Changes of Sleep Adaptation in Hospitalized Patients with Depression

Sleep adaptation in an unfamiliar environment, the so-called “first-night effect”, is known to occur in healthy individuals. To avoid the confounding effects of the “first-night effect”, the first-night sleep data are not used in most of sleep studies. In the present study, we examined changes of sleep adaptation in hospitalized patients with depression. Polysomnographic recordings were obtained for two consecutive nights from 14 patients, and sleep parameters were compared between both nights. Total sleep time, sleep latency, awakening times, movement awakening time, sleep efficiency, sleep architecture, rapid eye movement (REM) sleep latency, REM intensity, REM density, REM time, REM cycles, and other indicators showed no significant difference (p > 0.05) between the first and second nights. To conclude, hospitalized patients with depression have relatively less change in sleep adaptation, thus, the data from their first night do not need to be discarded.     

Tissue-Specific and Cation/Anion-Specific DNA Methylation Variations Occurred in C. virgata in Response to Salinity Stress

Salinity is a widespread environmental problem limiting productivity and growth of plants. Halophytes which can adapt and resist certain salt stress have various mechanisms to defend the higher salinity and alkalinity, and epigenetic mechanisms especially DNA methylation may play important roles in plant adaptability and plasticity. In this study, we aimed to investigate the different influences of various single salts (NaCl, Na₂SO₄, NaHCO₃, Na₂CO₃) and their mixed salts on halophyte Chloris. virgata from the DNA methylation prospective, and discover the underlying relationships between specific DNA methylation variations and specific cations/anions through the methylation-sensitive amplification polymorphism analysis. The results showed that the effects on DNA methylation variations of single salts were ranked as follows: Na₂CO₃> NaHCO₃> Na₂SO₄> NaCl, and their mixed salts exerted tissue-specific effects on C. virgata seedlings. Eight types of DNA methylation variations were detected and defined in C. virgata according to the specific cations/anions existed in stressful solutions; in addition, mix-specific and higher pH-specific bands were the main type in leaves and roots independently. These findings suggested that mixed salts were not the simple combination of single salts. Furthermore, not only single salts but also mixed salts showed tissue-specific and cations/anions-specific DNA methylation variations.     

The Complete Mitochondrial Genome of Gossypium hirsutum and Evolutionary Analysis of Higher Plant Mitochondrial Genomes

Background

Mitochondria are the main manufacturers of cellular ATP in eukaryotes. The plant mitochondrial genome contains large number of foreign DNA and repeated sequences undergone frequently intramolecular recombination. Upland Cotton (Gossypium hirsutum L.) is one of the main natural fiber crops and also an important oil-producing plant in the world. Sequencing of the cotton mitochondrial (mt) genome could be helpful for the evolution research of plant mt genomes.

Methodology/Principal Findings

We utilized 454 technology for sequencing and combined with Fosmid library of the Gossypium hirsutum mt genome screening and positive clones sequencing and conducted a series of evolutionary analysis on Cycas taitungensis and 24 angiosperms mt genomes. After data assembling and contigs joining, the complete mitochondrial genome sequence of G. hirsutum was obtained. The completed G.hirsutum mt genome is 621,884 bp in length, and contained 68 genes, including 35 protein genes, four rRNA genes and 29 tRNA genes. Five gene clusters are found conserved in all plant mt genomes; one and four clusters are specifically conserved in monocots and dicots, respectively. Homologous sequences are distributed along the plant mt genomes and species closely related share the most homologous sequences. For species that have both mt and chloroplast genome sequences available, we checked the location of cp-like migration and found several fragments closely linked with mitochondrial genes.

Conclusion

The G. hirsutum mt genome possesses most of the common characters of higher plant mt genomes. The existence of syntenic gene clusters, as well as the conservation of some intergenic sequences and genic content among the plant mt genomes suggest that evolution of mt genomes is consistent with plant taxonomy but independent among different species.