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miR-34b/c regulates doxorubicin-induced myocardial cell injury through ITcH

cELL cYcLE 2019年第23期18卷 3263-3274页

作者： Zhang, Wen-cai Yang, Jin-Hua Liu, Guang-Hui Yang, Fan Gong, Jun-Long Jia, Meng-Ge Zhang, Meng-Juan Zhao, Luo-Sha Zhengzhou Univ Dept Cardiol Affiliated Hosp 1 Zhengzhou Henan Peoples R China

Objective: To determine the underlying mechanism of miR-34b/c in regulating doxorubicin (Dox)-induced myocardial cell injury. Methods: The viability of mouse myocardial cells HL-1 was detected by MTT assay. The apoptosis of HL-1 cells was detected by TUNEL assay. mRNA expressions of ITcH, TNF-? and IL-6 were measured by qRT-PcR. Protein levels of ITcH, NF-?B, TNF-? and IL-6 were measured by western blot. Dual luciferase assay was performed to detect the regulation of miR-34b/c on ITcH. Mouse model of cardiomyopathy was induced by intraperitoneal injection of Dox. Results: Dox reduced HL-1 cell viability and activated NF-?B pathway in HL-1 cells. miR-34b/c expressions were gradually up-regulated and ITcH expression was gradually down-regulated in Dox-treated HL-1 cells. miR-34b/c expression had negative correlation with the mRNA expression of ITcH. Besides, ITcH was a target of miR-34b/c. miR-34b/c mimic reduced cell viability, suppressed ITcH expression, increased TNF-? and IL-6 level, and promoted NF-?B expression in nucleus and cytoplasm of HL-1 cells. Whereas silencing miR-34 protected HL-1 cells through regulating ITcH. Finally, we demonstrated miR-34 antagomir-protected myocardial cells in mouse model of cardiomyopathy. conclusion: miR-34b/c decreased HL-1 cell viability and promoted the secretion of proinflammatory cytokines in Dox-induced myocardial cells through ITcH/NF-?B pathway.

关键词： Doxorubicin miR-34b c ITcH NF-?B myocardial cell

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New c,O-Glycosylflavones from Melandrium divaricatum

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cHEMISTRY OF NATURAL cOMPOUNDS 2019年第6期55卷 1032-1038页

作者： Olennikov, D. N. chirikova, N. K. Russian Acad Sci Inst Gen & Expt Biol Siberian Branch 6 Sakhyanovoi St Ulan Ude 670047 Russia MK Ammosov North Eastern Fed Univ 58 Belinskogo St Yakutsk 677000 Russia

The aerial part of Melandrium divaricatum Fenzl (caryophyllaceae) afforded 11 glycosylflavones including two new compounds that were characterized using UV, IR, and NMR spectroscopy and mass spectrometry as apigenin-6-c-(2 '' -O-alpha-L-rhamnopyranosyl)-beta-D-glucopyranoside-7-O-(6 '''' -O-feruloyl)-beta-Dglucopyranoside (divarioside A, 1) and apigenin-6-c-(2 ''-O-D-glucopyranosyl)- beta-D-glucopyranoside-7-O-(6 ''''-O-feruloyl)- beta-D-glucopyranoside (divarioside B, 2).

关键词： Melandrium divaricatum c O-glycosylflavones divarioside HPLc

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Effects of high and low c:P foods on the feeding of Daphnia pulex

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JOURNAL OF FRESHWATER EcOLOGY 2019年第1期34卷 455-468页

作者： Guo, Nichun Li, Mingyuan Tian, Haotong Ma, Youhua Anhui Agr Univ Sch Resources & Environm Hefei 230036 Anhui Peoples R China Anhui Agr Univ New Rural Dev Res Inst Hefei Anhui Peoples R China

The effects of food quality and food quantity on crustacean zooplankton's feeding rate have been analyzed in the present study. In two experiments, we studied the clearance rates (cRs) of Daphnia pulex on different algal diets (Scenedesmus obliquus, nontoxic Microcystis sp. Pcc7806 and Anabeana flos-aquae) varying in carbon to phosphorus (c:P) ratios and quantities (concentrations). In order to investigate the effects of different algal diets on the feeding of cladocerans, the mixture of S. obliquus, Microcystis sp. Pcc7806 and A. flos-aquae was also fed to D. pulex during a 72-h period. Our results showed: (1) D. pulex had different clearance rates from the three mono-specific P-rich algal diets, while no significant difference among clearance rates was observed among the three mono-specific P-poor algal diets;(2) D. pulex increased its clearance rates when it fed on mono-specific P-poor S. obliquus and A. flos-aquae, while a P-poor mixture of M. aeruginosa and A. flos-aquae reduced the clearance rate;(3) A U-shaped quadratic function provided a good fit to the clearance rate and c:P ratios because the clearance rate of D. pulex in both low and high c:P categories were significantly higher than in the moderate c:P category (c:P value = 219). Our results demonstrated that filaments and c:P ratios of algae strongly influence the feeding of crustacean zooplankton. 'compensatory feeding' occurred in the mono-specific, P-poor algal diets but not in the mixed diets. Moreover, the clearance rate of zooplankton was the lowest in the moderate P stoichiometric category. Our experiments suggest that the morphology and c:P ratios of algal diets have important effects on the feeding of Daphnia, and the P stoichiometric characteristics in mixed diets may play an important role in the feeding of large-sized cladocerans.

关键词： Food quality Daphnia pulex clearance rate filament c P ratios

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Synthesis of Functional carbo -benzenes with Functional Properties: The c 2 Tether Key

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SYNLETT 2019年第1期30卷 30-43页

作者： cocq, Kevin Barthes, cecile Rives, Arnaud Maraval, Valerie chauvin, Remi CNRS LCC 205 Route NarbonneBP44099 F-31077 Toulouse 4 France Univ Toulouse UPS ICT FR 2599 F-31062 Toulouse 9 France

Beyond demonstration of conceptual relevance and synthetic feasibility of aryl/alkyl-substituted representatives, carbo -benzene molecules started to gain prospects of broader impact through the emergence of alkynyl derivatives. This is first illustrated by examples of di- and hexaalkynyl- carbo -benzenes, a carbo -naphthalene, a carbo -biphenyl, and two carbo -terphenyls. A focus is then given to dialkynyl derivatives by reference to the peripherally c (2) -extruded parents. In the centrosymmetric quadrupolar series, the c (2) expansion or ethynylogation effect is more particularly considered for 9 H -fluoren-2-yl, tris(O- n -alkyl)pyrogallyl, indol-3-yl, 4-anilinyl, and tetraphenyl- carbo -phenyl substituents on the following respective properties: two-photon absorption, chemical stability, columnar mesogenicity, on-surface photoinduced charge separation vs single-molecule conductance, and reduction potential. Topical results and prospects of application are discussed on the basis of crystallographic, spectroscopic, and electrochemical analyses vs DFT-calculated nuclear and electronic structures. For the sake of the discussion consistency, complementary experimental and computational results are disclosed in the dianilinyl series. Overall, it is shown that combined advances in strategy, protocols, and substrate scope of acetylenic synthesis remain crucial for the development of yet poorly explored but promising types of molecular materials. 1Introduction 2Hexaalkynyl- carbo -benzene 3 ortho -Dialkynyl- carbo -benzene 4 para -Dialkynyl- carbo -benzenes 4.1Bistrimethylsilylethynyl- carbo -benzene 4.2Bisfluorenylethynyl- carbo -benzene 4.3Bistrialkoxyarylethynyl- carbo -benzenes 4.4Bisindolylethynyl- carbo -benzene 4.5Bisanilinylethynyl- carbo -benzene 5 carbo -oligo(phenyleneethynylene)s 6conclusions

关键词： alkyne c (2) tether carbo -benzene carbo -mer pi-conjugation

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A c-elegans Model for the Study of RAGE-Related Neurodegeneration

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NEUROTOXIcITY RESEARcH 2019年第1期35卷 19-28页

作者： Pinkas, Adi Lee, Kun He chen, Pan Aschner, Michael Albert Einstein Coll Med Jack & Pearl Resnick Campus1300 Morris Pk Ave Bronx NY 10461 USA

The receptor for advanced glycation products (RAGE) is a cell surface, multi-ligand receptor belonging to the immunoglobulin superfamily;this receptor is implicated in a variety of maladies, via inflammatory pathways and induction of oxidative stress. currently, RAGE is being studied using a limited number of mammalian in vivo, and some complementary in vitro, models. Here, we present a caenorhabditis elegans model for the study of RAGE-related pathology: a transgenic strain, expressing RAGE in all neurons, was generated and subsequently tested behaviorally, developmentally, and morphologically. In addition to RAGE expression being associated with a significantly shorter lifespan, the following behavioral observations were made when RAGE-expressing worms were compared to the wild type: RAGE-expressing worms showed an impaired dopaminergic system, evaluated by measuring the fluorescent signal of GFP tagging;these worms exhibited decreased locomotionboth general and following ethanol exposureas measured by counting body bends in adult worms;RAGE expression was also associated with impaired recovery of quiescence and pharyngeal pumping secondary to heat shock, as a significantly smaller fraction of RAGE-expressing worms engaged in these behaviors in the 2h immediately following the heat shock. Finally, significant developmental differences were also found between the two strains: RAGE expression leads to a significantly smaller fraction of hatched eggs 24h after laying and also to a significantly slower developmental speed overall. As evidence for the role of RAGE in a variety of neuropathologies accumulates, the use of this novel and expedient model should facilitate the elucidation of relevant underlying mechanisms and also the development of efficient therapeutic strategies.

关键词： RAGE c elegans Behavior Neurodegeneration Development

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Real life efficacy and safety of direct-acting antiviral therapy for treatment of patients infected with hepatitis c virus genotypes 1, 2and 3 in northwest china

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World Journal of Gastroenterology 2019年第44期25卷 6551-6560页

作者： Ying Yang Feng-Ping Wu Wen-Jun Wang Juan-Juan Shi Ya-Ping Li Xin Zhang Shuang-Suo Dang Department of Infectious Diseases the Second Affiliated Hospital of Xi’an Jiaotong University

BAcKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis c virus(HcV)genotypes 1,2 and *** real-world data is still not enough,especially in *** To investigate the efficacy and safety of DAA-based regimens in a real-life setting in *** This study included 366 patients infected with HcV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December *** were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more *** participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary *** occurrence of adverse events and drug-drug interactions were *** In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)***(13.7%)patients were ***-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype *** of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HcV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the

关键词： Hepatitis c virus Direct-acting antiviral agents Efficacy Safety Drug-drug interactions Real-life experience

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Hypermethylation of the G protein-coupled receptor kinase 6 (GRK6) promoter inhibits binding of c/EBP, and GRK6 knockdown promotes cell migration and invasion in lung adenocarcinoma cells

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FEBS OPEN BIO 2019年第4期9卷 605-617页

作者： Yao, Sumei Wu, Dandan chen, Jinliang Wang, Peng Lv, Xuedong Huang, Jianan Soochow Univ Affiliated Hosp 1 Dept Resp 188 Shizi Rd Suzhou 215006 Jiangsu Peoples R China Nantong Univ Affiliated Hosp 2 Dept Resp Nantong Peoples R China

We previously reported that the expression of G protein-coupled receptor kinase 6 (GRK6) is significantly downregulated in lung adenocarcinoma (LADc) tissues, and low expression levels of GRK6 are correlated with poor survival prognosis. However, the specific regulatory mechanisms and functions of GRK6 in LADc remain unknown. Here, we report that GRK6 mRNA expression levels are downregulated in LADc tissues compared to those in matched adjacent non-tumor tissues (P<0.001). The promoter of the GRK6 gene was found to be hypermethylated in LADc tissues, and its methylation was correlated with both GRK6 expression and pathology grade. GRK6 promoter hypermethylation may predict shorter overall survival. Treatment with 5-aza-2-deoxycytidine significantly enhanced GRK6 gene expression. Four binding sites of ccAAT/enhancer-binding protein- (c/EBP) in the cpG island of the GRK6 gene promoter were predicted insilico, of which three sites were further confirmed by chIP. Decreased binding of c/EBP to binding sites 1, 3 and 4 of the GRK6 gene promoter was observed in LADc tissues. Inhibition of c/EBP significantly inhibited GRK6 expression, while overexpression of c/EBP significantly promoted GRK6 expression. In addition, overexpression of GRK6 significantly suppressed, while GRK6 knockdown promoted cell migration and invasion. Overexpression of GRK6 enhanced E-cadherin expression and suppressed vimentin expression, and silencing of GRK6 had the opposite effects. Furthermore, ectopic expression of GRK6 significantly decreased matrix metalloproteinase (MMP) 2 and MMP7 protein expression levels. Our findings suggest that hypermethylation of the GRK6 gene promoter suppressed binding of c/EBP, thereby contributing to the promotion of cell migration and invasion. The methylation status of the GRK6 promoter might be suitable for use as an epigenetic biomarker, and the c/EBP-GRK6 signaling pathway may be a potential target for LADc.

关键词： c EBP DNA methylation epigenetic regulation GRK6 lung adenocarcinoma

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Predicting nitrogen mineralization from organic amendments: beyond c/N ratio by ¹³c-cPMAS NMR approach

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PLANT AND SOIL 2019年第1-2期441卷 129-146页

作者： Bonanomi, Giuliano Sarker, Tushar c. Zotti, Maurizio cesarano, Gaspare Allevato, Emilia Mazzoleni, Stefano Univ Naples Federico II Dipartimento Agr Via Univ 100 I-80055 Portici NA Italy Zhejiang A&F Univ Sch Environm & Resource Sci Hangzhou 311300 Zhejiang Peoples R China

Background and aim The processes of nitrogen (N) mineralization from organic amendments (OA) is important to provide mineral forms (NH4+ and NO3-) of N for plants. Assessment of N mineralization is usually done by using the c/N ratio of OAs but limits to the predicting capability of such indicator have been reported. Here, we propose a new definition of organic carbon (c) quality based on c-13-cPMAS NMR that provide a more accurate prediction of N mineralization. Methods A mesocosm incubation experiment was carried out to assess the effects of ten OA types on soil N mineralization in three different soils. OAs were chemically characterized by c/N ratio and in solid state spectroscopy by c-13-cPMAS NMR. Nitrogen mineralization in terms of NH4+ and NO3- was monitored after 3, 10, 30, 100, and 300 days of incubation. Results N mineralization was fast for OAs with high c quality coupled with high N content (e.g., meat powder, fish meal and alfalfa litter), while the same process was slow for amendment with low c quality even with high N content (e.g. humus, alfalfa biochar). On the contrary, a rapid but short-term N immobilization was found for OAs with high c quality but low N content (e.g., glucose). OAs with low c quality and low N content (e.g., sawdust, cellulose, wood biochar and grass litter) showed a slow, but long-lasting N immobilization. We found that c/N ratio was unable to predict the N mineralization for OAs with low c quality. considering c-13-cPMAS NMR spectral regions, the carbonyl c, and N-alkyl and methoxyl c regions had the most significant positive correlation with N mineralization, while the di-O-alkyl c and O-alkyl c were strongly associated with N immobilization. conclusions This study demonstrates that the biochemical quality of organic c defined by c-13-cPMAS NMR is capable of predicting N dynamic pattern better than c/N ratio.

关键词： N mineralization Organic amendment c N ratio c-13-cPMAS NMR Soil quality

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Enhanced monocyte recruitment and delayed alternative macrophage polarization accompanies impaired repair following myocardial infarction in c57BL/6 compared to BALB/c mice

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cLINIcAL AND EXPERIMENTAL IMMUNOLOGY 2019年第1期198卷 83-93页

作者： Toor, I. S. Ruckerl, D. Mair, I. Thomson, A. Rossi, A. G. Newby, D. E. Allen, J. E. Gray, G. A. Univ Edinburgh Queens Med Res Inst BHF Univ Ctr Cardiovasc Sci 47 Little France Crescent Edinburgh EH16 4TJ Midlothian Scotland Univ Manchester Fac Biol Med & Hlth Sch Biol Sci Manchester Lancs England Univ Edinburgh Queens Med Res Inst MRC Ctr Inflammat Res Edinburgh Midlothian Scotland

Activation of the innate immune response following myocardial infarction (MI) is essential for infarct repair. Preclinical models of MI commonly use c57BL/6 mice, which have a type 1-dominant immune response, whereas other mouse strains such as BALB/c mice have a type 2-dominant immune response. We compared c57BL/6 and BALB/c mice to investigate whether predisposition towards a proinflammatory phenotype influences the dynamics of the innate immune response to MI and associated infarct healing and the risk of cardiac rupture. MI was induced by permanent coronary artery ligation in 12-15-week-old male wild-type BALB/c and c57BL/6 mice. Prior to MI, c57BL/6 mice had a lower proportion of cD206(+) anti-inflammatory macrophages in the heart and an expanded blood pool of proinflammatory Ly6c(high) monocytes in comparison to BALB/c mice. The systemic inflammatory response in c57BL/6 mice following MI was more pronounced, with greater peripheral blood Ly6c(high) monocytosis, splenic Ly6c(high) monocyte mobilization and myeloid cell infiltration of pericardial adipose tissue. This led to an increased and prolonged macrophage accumulation, as well as delayed transition towards anti-inflammatory macrophage polarization in the infarct zone and surrounding tissues of c57BL/6 mice. These findings accompanied a higher rate of mortality due to cardiac rupture in c57BL/6 mice compared with BALB/c mice. We conclude that lower post-MI survival of c57BL/6 mice over BALB/c mice is mediated in part by a more pronounced and prolonged inflammatory response. Outcomes in BALB/c mice highlight the therapeutic potential of modulating resolution of the innate immune response following MI for the benefit of successful infarct healing.

关键词： c57BL 6 BALB c macrophage polarization monocyte myocardial infarction

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Effects of FUdR on gene expression in the c. elegans bacterial diet OP50

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BMc RESEARcH NOTES 2021年第1期14卷 207-207页

作者： McIntyre, Grace Wright, Justin Wong, Hoi Tong Lamendella, Regina chan, Jason Marian Univ Dept Biol 3200 Cold Spring Rd Indianapolis IN 46222 USA Juniata Coll Dept Biol 1700 Moore St Huntingdon PA 16652 USA

Objective Many c. elegans aging studies use the compound 5-fluro-2MODIFIER LETTER PRIME-deoxyuridine (FUdR) to produce a synchronous population of worms. However, the effects of FUdR on the bacterial gene expression of OP50 E. coli, the primary laboratory c. elegans food source, is not fully understood. This is particularly relevant as studies suggest that intestinal microbes can affect c. elegans physiology. Therefore, it is imperative that we understand how exposure to FUdR can affect gene expression changes in OP50 E. coli. Results An RNAseq dataset comprised of expression patterns of 2900 E. coli genes in the strain OP50, which were seeded on either nematode growth media (NGM) plates or on FUdR (50 mu M) supplemented NGM plates, was analyzed. Analysis showed differential gene expression in genes involved in general transport, amino acid biosynthesis, transcription, iron transport, and antibiotic resistance. We specifically highlight metabolic enzymes in the l-histidine biosynthesis pathway as differentially expressed between NGM and FUdR exposed OP50. We conclude that OP50 exposed to FUdR results in differential expression of many genes, including those in amino acid biosynthetic pathways.

关键词： c elegans E coli FUdR Aging Bacterial transcriptomics

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