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Chronic inhibition of cyclic guanosine monophosphate-specific phosphodiesterase 5 prevented cardiac fibrosisthrough inhibition of transforming growth factor β-induced Smad signaling

null

《医学前沿(英文)》 2014年 第8卷 第4期   页码 445-455 doi: 10.1007/s11684-014-0378-3

摘要:

Recent evidences suggested that cyclic guanosine monophosphate-specific phosphodiesterase 5 (PDE5) inhibitor represents an important therapeutic target for cardiovascular diseases. Whether and how it ameliorates cardiac fibrosis, a major cause of diastolic dysfunction and heart failure, is unknown. The purpose of this study was to investigate the effects of PDE5 inhibitor on cardiac fibrosis. We assessed cardiac fibrosis and pathology in mice subjected to transverse aortic constriction (TAC). Oral sildenafil, a PDE5 inhibitor, was administered in the therapy group. In control mice, 4 weeks of TAC induced significant cardiac dysfunction, cardiac fibrosis, and cardiac fibroblast activation (proliferation and transformation to myofibroblasts). Sildenafil treatment markedly prevented TAC-induced cardiac dysfunction, cardiac fibrosis and cardiac fibroblast activation but did not block TAC-induced transforming growth factor-β1 (TGF-β1) production and phosphorylation of Smad2/3. In isolated cardiac fibroblasts, sildenafil blocked TGF-β1-induced cardiac fibroblast transformation, proliferation and collagen synthesis. Furthermore, we found that sildenafil induced phosphorylated cAMP response element binding protein (CREB) and reduced CREB-binding protein 1 (CBP1) recruitment to Smad transcriptional complexes. PDE5 inhibition prevents cardiac fibrosis by reducing CBP1 recruitment to Smad transcriptional complexes through CREB activation in cardiac fibroblasts.

关键词: PDE5     cardiac fibrosis     TGF-β     CREB    

simultaneous anammox and denitrification system with short-term pyridine exposure: Process capability, inhibition

《环境科学与工程前沿(英文)》 2021年 第15卷 第6期 doi: 10.1007/s11783-021-1433-3

摘要:

• Short-term effect of the pyridine exposure on the SAD process was investigated.

关键词: Anammox     Inhibition     Metabolic pathway     Microbial community     Pyridine     SAD    

ROOT EXUDATES FROM CANOLA EXHIBIT BIOLOGICAL NITRIFICATION INHIBITION AND ARE EFFECTIVE IN INHIBITING

《农业科学与工程前沿(英文)》 2022年 第9卷 第2期   页码 177-186 doi: 10.15302/J-FASE-2021421

摘要:

A range of plant species produce root exudates that inhibit ammonia-oxidizing microorganisms. This biological nitrification inhibition (BNI) capacity can decrease N loss and increase N uptake from the rhizosphere. This study sought evidence for the existence and magnitude of BNI capacity in canola ( Brassica napus). Seedlings of three canola cultivars, Brachiaria humidicola(BNI positive) and wheat ( Triticum aestivum) were grown in a hydroponic system. Root exudates were collected and their inhibition of the ammonia oxidizing bacterium, Nitrosospira multiformis, was tested. Subsequent pot experiments were used to test the inhibition of native nitrifying communities in soil. Root exudates from canola significantly reduced nitrification rates of both N. multiformis cultures and native soil microbial communities. The level of nitrification inhibition across the three cultivars was similar to the well-studied high-BNI species B. humidicola. BNI capacity of canola may have implications for the N dynamics in farming systems and the N uptake efficiency of crops in rotational farming systems. By reducing nitrification rates canola crops may decrease N losses, increase plant N uptake and encourage microbial N immobilization and subsequently increase the pool of organic N that is available for mineralization during the following cereal crops.

关键词: ammonia oxidizing microorganisms / biological nitrification inhibition / farming rotations / nitrogen cycling / nitrogen use efficiency    

Inhibition character of crotonaldehyde manufacture wastewater on biological acidification

《环境科学与工程前沿(英文)》 2021年 第15卷 第6期 doi: 10.1007/s11783-021-1403-9

摘要:

• The inhibition of the main organic pollutions in CMW was demonstrated.

关键词: Crotonaldehyde manufacture wastewater     Biological acidification     Volatile fatty acids     Inhibition     Toxic units    

Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition

null

《医学前沿(英文)》 2016年 第10卷 第3期   页码 311-319 doi: 10.1007/s11684-016-0460-0

摘要:

We evaluated the roles of calpain cleavage-related mutations of the integrin β3 cytoplasmic tail in integrin αIIbβ3 bidirectional signaling using a trans-dominant inhibition model. Chimeric Tac-β3 proteins (i.e., Tac-β3, Tac-β3D741, Tac-β3D747, Tac-β3D754, Tac-β3D759, and Tac-β3DNITY) consisting of the extracellular and transmembrane domains of human IL-2 receptor (Tac) and the human integrin β3 cytoplasmic domain were stably expressed in the 123 CHO cells harboring human glycoprotein Ib-IX and wild-type integrin αIIbβ3. The different cells were assayed for stable adhesion and spreading on immobilized fibrinogen, and for binding soluble fibrinogen representing outside-in and inside-out signaling events, respectively. The chimeric protein Tac-β3 inhibited, and Tac-β3DNITY partially attenuated stable adhesion and spreading. Tac-β3, Tac-β3D759, Tac-β3DNITY, and Tac-β3D754, but not Tac-β3D747 or Tac-β3D741, impaired the soluble fibrinogen binding. Results indicated that the bidirectional signaling was significantly inhibited by Tac-β3 and Tac-β3DNITY, albeit to a much lesser extent. Moreover, only inside-out signaling was impaired in the 123/Tac-β3D759 and 123/Tac-β3D754 cells in contrast to an intact bidirectional signaling in the 123/Tac-β3D747 and 123/Tac-β3D741 cells. In conclusion, the calpain cleavage of integrin β3 resulted in the regulatory effects on signaling by interrupting its interaction with cytoplasmic proteins rather than altering its conformation, and may thus regulate platelet function.

关键词: integrin β3     signal transduction     trans-dominant inhibition model    

Head-to-tail cyclization of a heptapeptide eliminates its cytotoxicity and significantly increases its inhibition

Shuai Ma, Huan Zhang, Xiaoyan Dong, Linling Yu, Jie Zheng, Yan Sun

《化学科学与工程前沿(英文)》 2018年 第12卷 第2期   页码 283-295 doi: 10.1007/s11705-017-1687-2

摘要: Amyloid- (A ) protein aggregation is the main hallmark of Alzheimer’s disease (AD). Inhibition of A fibrillation is thus a promising therapeutic approach to the prevention and treatment of AD. Recently, we designed a heptapeptide inhibitor, LVFFARK (LK7). LK7 shows a promising inhibitory capability on A fibrillation, but is prone to self-assembling and displays high cytotoxicity, which would hinder its practical application. Herein, we modified LK7 by a head-to-tail cyclization and obtained a cyclic LK7 (cLK7). cLK7 exhibits a different self-assembly behavior from LK7, and has higher stability against proteolysis than LK7 and little cytotoxicity to SH-SY5Y cells. Thermodynamic analysis revealed that both LK7 and cLK7 could bind to A by electrostatic interactions, hydrogen bonding and hydrophobic interactions, but the binding affinity of cLK7 for A ( = 4.96 µmol/L) is six times higher than that of LK7 ( = 32.2 µmol/L). The strong binding enables cLK7 to stabilize the secondary structure of A and potently inhibit its nucleation, fibrillation and cytotoxicity at extensive concentration range, whereas LK7 could only moderately inhibit A fibrillation and cytotoxicity at low concentrations. The findings indicate that the peptide cyclization is a promising approach to enhance the performance of peptide-based amyloid inhibitors.

关键词: Alzheimer’s disease     amyloid β-protein     cyclic peptide     inhibition     protein aggregation    

Effects of galectin-3 inhibition on endometrial cell cycle and adhesion

LEI Caixia, ZHANG Wei, SUN Xiaowei, DU Guoping, WANG Li, LIU Yinkun

《医学前沿(英文)》 2007年 第1卷 第4期   页码 390-397 doi: 10.1007/s11684-007-0076-5

摘要: Galectin-3 (gal-3) and its ligands have been implicated in cell transformation and cancer metastasis. Gal-3 protein has been found in uterine epithelial cells adjacent to implanting blastocysts in different cell types. In order to investigate the role of gal-3 in the establishment of human endometrial receptivity, the expression of gal-3 in human endometrial cell line RL95-2 was silenced by RNA interference technology using gal-3 specific small RNA. The expression of gal-3 was detected by the reverse transcriptase-polymerase chain reaction and Western blot analysis. After the suppression of gal-3, cell cycle changes and the expression of integrin 1 were detected by flow cytometry. The adhesive ability of RL95-2 cells was analyzed by the adhesion test. Gal-3 siRNA transfection efficiency reached 70%–90%. The expression of gal-3 mRNA and protein in RL95-2 cells was strongly inhibited by 70%–90% after RNA interference. Inhibition of gal-3 expression decreased S-phase but increased G1 phase cells. Integrin 1 expression was down-regulated, and the adhesive ability of RL95-2 cells to fibronectin (FN) was significantly reduced. Gal-3 may be involved in the establishment of endometrial receptivity by regulating the proliferation and adhesion of endometrial cells. The influence on adhesion may be related with the integrin modulation.

Comparison in executive function in Chinese preterm and full-term infants at eight months

null

《医学前沿(英文)》 2018年 第12卷 第2期   页码 164-173 doi: 10.1007/s11684-017-0540-9

摘要:

Executive function (EF) is increasingly recognized as being responsible for adverse developmental outcomes in preterm-born infants. Several perinatal factors may lead to poor EF development in infancy, and the deficits in EF can be identified in infants as young as eight months. A prospective cohort study was designed to study the EF in Chinese preterm infants and examine the relationship between EF in preterm infants and maternal factors during perinatal period. A total of 88 preterm infants and 88 full-term infants were followed from birth to eight months (corrected age). Cup Task and Planning Test was applied to assess the EF of infants, and the Bayley Scale of Infant Development (BSID-III) was used to evaluate cognitive (MDI) and motor abilities (PDI) of infants. In comparison with full-term infants, the preterm infants performed more poorly on all measures of EF including working memory, inhibition to prepotent responses, inhibition to distraction, and planning, and the differences remained after controlling the MDI and PDI. Anemia and selenium deficiency in mothers during pregnancy contributed to the differences in EF performance. However, maternal depression, hypertension, and diabetes during pregnancy were not related to the EF deficits in preterm infants. Future research should focus on the prevention of anemia and selenium deficiency during pregnancy and whether supplementing selenium in mothers during pregnancy can prevent further deterioration and the development of adverse outcomes of their offspring.

关键词: executive function (EF)     preterm infant     working memory     inhibition to prepotent response     inhibition to distraction     planning    

Allelopathic inhibition on red tide microalgae by five macroalgal extracts

AN Zhen, WANG Zhenyu, LI Fengmin, TIAN Zhijia, HU Hongying

《环境科学与工程前沿(英文)》 2008年 第2卷 第3期   页码 297-305 doi: 10.1007/s11783-008-0055-3

摘要: This study aims to identify effective antialgal allelochemicals from marine macroalgae that inhibit the growth of red tide microalgae. Practically, new algicidal agents were developed to control red tide. The growth inhibitory effects of 5 marine macroalgae , , , , and on were evaluated by adding crude seawater extracts of macroalgal dry tissue into the culture medium containing . The half-effective concentrations at 120 h (EC) of the seawater extracts were 0.6, 0.9, 1.0, 1.0, and 4.7 g/L for the five macroalgae above, respectively. , and showed strong allelopathic effect on the growth of . There have been no previous reports with regard to the allelopathic effects of the former two macroalgae so far. The possible allelochemicals of 21 compounds of the were detected using Gas chromatography-mass spectrometry (GC-MS) analysis. Unsaturated fatty acids, acrylic acid (CHO), and linolenic acid (CHO) were the most likely allelochemicals in .

关键词: containing     linolenic     inhibitory     microalgae     Practically    

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

《医学前沿(英文)》 2015年 第9卷 第2期   页码 134-138 doi: 10.1007/s11684-015-0396-9

摘要:

Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

关键词: targeted therapy     drug resistance     receptor tyrosine kinases     cancer    

Long acting carmustine loaded natural extracellular matrix hydrogel for inhibition of glioblastoma recurrence

《化学科学与工程前沿(英文)》 2022年 第16卷 第4期   页码 536-545 doi: 10.1007/s11705-021-2067-5

摘要: Many scientific efforts have been made to penetrate the blood-brain barrier and target glioblastoma cells, but the outcomes have been limited. More attention should be given to local inhibition of recurrence after glioblastoma resection to meet real medical needs. A biodegradable wafer containing the chemotherapeutics carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU) was the only local drug delivery system approved for clinical glioblastoma treatment, but with a prolonged survival time of only two months and frequent side effects. In this study, to improve the sustained release and prolonged therapeutic effect of drugs for inhibiting tumor recurrence after tumor resection, both free BCNU and BCNU- poly (lactic-co-glycolic acid) (the ratio of lactic acid groups to glycolic acid groups is 75/25) nanoparticles were simultaneously loaded into natural extracellular matrix hydrogel from pigskin to prepare BCNU gels. The hydrogel was injected into the resection cavity of a glioblastoma tumor immediately after tumor removal in a fully characterized resection rat model. Free drugs were released instantly to kill the residual tumor cells, while drugs in nanoparticles were continuously released to achieve a continuous and effective inhibition of the residual tumor cells for 30 days. These combined actions effectively restricted tumor growth in rats. Thus, this strategy of local drug implantation and delivery may provide a reliable method to inhibit the recurrence of glioblastoma after tumor resection in vivo.

关键词: BCNU     glioblastoma recurrence     tumor resection     nanoparticles     hydrogel    

Synergistic scale inhibition of polyaspartic acid composite with magnetic field

LIU Zhenfa, WANG Yanji, GAO Yuhua, ZHANG Lihui

《化学科学与工程前沿(英文)》 2007年 第1卷 第3期   页码 261-265 doi: 10.1007/s11705-007-0047-z

摘要: Polyaspartic acid (PASP) composite, a scale inhibitor, was prepared from PASP, itaconic acid–acrylic acid–acrylic ester (IA-AA-AE) terpolymer and 2-phosphonobutane- 1,2,4-tricarboxylic acid (PBTCA). The scale inhibition of PASP composite and the effect of its synergism with a magnetic field on scale inhibition were investigated. Calcium carbonate crystals in scale samples were characterized by means of SEM and XRD. The static and dynamic experiments show that the chelating function of PASP composite for Ca can be enhanced by synergism with a magnetic field. Under Ca 650 mg/L, HCO 1,300 mg/L and PASP composite 4 mg/L, the scale inhibition rate of PASP composite in magnetic water can increase by 10% in static state and by 20% in dynamic experiments. Scanning electron microscope (SEM) and X-ray diffraction (XRD) results show that calcite and aragonite can be completely transformed into vaterite by using PASP composite.

关键词: synergism     magnetic     PBTCA     dynamic     acid–acrylic acid–acrylic    

Inhibition of NO emission by adding antioxidant mixture in

A. PRABU,R. B. ANAND

《能源前沿(英文)》 2015年 第9卷 第2期   页码 238-245 doi: 10.1007/s11708-015-0356-8

摘要: In this paper, the effect of adding an antioxidant mixture in biodiesel as fuel, in a single cylinder, direct injection compression ignition engine was experimentally investigated and the level of pollutants in the exhaust and performance characteristics of the engine were analyzed. Nine test fuels were prepared with three antioxidants, namely, Succinimide (C H NO ), , dimethyl- -phenylenediamine-dihydrochloride (C H Cl N ), and -phenyl- -phenylenediamine (C H NHC H NH ) added to neat biodiesel at 500 parts per million (ppm), 1000 ppm and 2000 ppm and the observed experimental results were compared with those of neat biodiesel and neat diesel as base fuels. The comparison showed that NO emission was reduced drastically for the test fuels with the antioxidant addition of 2000 ppm. The maximum reduction of 10% of NO emission was observed for the antioxidant mixture in neat biodiesel, with a slight increase in unburned HC, CO and smoke opacity. In addition, the obtained experimental results reveal that the addition of two antioxidants as mixture in neat biodiesel caused improved NO emission reduction for all test fuels.

关键词: NO emission     antioxidants     Succinimide     N     N-dimethyl-p-phenylenediamine-dihydrochloride     N-phenyl-p-phenylenediamine    

钨矿物原料NaOH分解过程中抑制杂质的研究

李洪桂,李运姣,孙培梅,刘茂盛

《中国工程科学》 2000年 第2卷 第3期   页码 59-61

摘要:

从理论上较全面地研究了钨矿物原料在NaOH分解过程中直接用白钨矿及其分解产物Ca(OH)2作为抑制剂,抑制磷、砷、硅等杂质浸出的可能性及生成物的形态。进而通过实验证明在有白钨矿存在的条件下,分解所得的粗Na2WO4溶液中砷、硅的含量均比经典法低一个数量级,接近经典法净化以后的水平。

关键词: 钨冶金     NaOH分解     抑制杂质    

Absence of FHIT expression is associated with apoptosis inhibition in colorectal cancer

CAO Jie, LI Wanglin, XIA Jie, TANG Weibiao, WANG Hui, CHEN Xiwen, XIAO Huanqing, LI Yuyuan, CHEN Xiaoping, DU Hong, CHEN Shanming

《医学前沿(英文)》 2007年 第1卷 第2期   页码 147-156 doi: 10.1007/s11684-007-0028-0

摘要: The fragile histidine triad (FHIT) gene, a candidate tumor suppressor gene located at 3p14.2, has been shown to be involved in the carcinogenesis of many human tissues, including digestive tract tissues. However, the expression and the role of the FHIT in the initiation and the development of the colorectal cancer (CRC) are poorly understood. We have shown that the FHIT gene exhibits significantly decreased expression in human CRC compared to colorectal adenoma and normal colorectal tissue by tissue microarray (TMA). The positive rate of FHIT gene expression in normal colorectal tissue, adenoma and adenocarcinoma were 93.75%, 68.75% and 46.25%, respectively. We show this decreased expression to be significantly correlated with the progression of colorectal carcinoma (<0.05) as well as with differentiation and lymph node metastasis (<0.05). We detected two somatic alterations in the FHIT gene in human CRC. The presence of this mutation correlated significantly with decreased FHIT expression in the human CRC. In our present study we tested the hypothesis that the decreased FHIT expression resulted in apoptosis inhibition associated with abnormal expression of apoptosis related proteins. To test this hypothesis we did a series of experiments. In the first test, we assessed apoptosis status using a standard TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling) assay by comparing FHIT-positive CRC vs. FHIT-negative CRC. In the second experiment, the protein expression of the FHIT and other apoptosis related proteins (Bax, Bcl-2 and Survivin) were measured in human CRC by TMA. Our combined results demonstrate the mutation in the FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and the up-regulation of Survivin and Bcl-2. Collectively, these studies identify the mechanism by which an important tumor suppressor gene, FHIT is inactivated specifically in human CRC contributing to our understanding of the mechanism of colorectal carcinogenesis.

标题 作者 时间 类型 操作

Chronic inhibition of cyclic guanosine monophosphate-specific phosphodiesterase 5 prevented cardiac fibrosisthrough inhibition of transforming growth factor β-induced Smad signaling

null

期刊论文

simultaneous anammox and denitrification system with short-term pyridine exposure: Process capability, inhibition

期刊论文

ROOT EXUDATES FROM CANOLA EXHIBIT BIOLOGICAL NITRIFICATION INHIBITION AND ARE EFFECTIVE IN INHIBITING

期刊论文

Inhibition character of crotonaldehyde manufacture wastewater on biological acidification

期刊论文

Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition

null

期刊论文

Head-to-tail cyclization of a heptapeptide eliminates its cytotoxicity and significantly increases its inhibition

Shuai Ma, Huan Zhang, Xiaoyan Dong, Linling Yu, Jie Zheng, Yan Sun

期刊论文

Effects of galectin-3 inhibition on endometrial cell cycle and adhesion

LEI Caixia, ZHANG Wei, SUN Xiaowei, DU Guoping, WANG Li, LIU Yinkun

期刊论文

Comparison in executive function in Chinese preterm and full-term infants at eight months

null

期刊论文

Allelopathic inhibition on red tide microalgae by five macroalgal extracts

AN Zhen, WANG Zhenyu, LI Fengmin, TIAN Zhijia, HU Hongying

期刊论文

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

期刊论文

Long acting carmustine loaded natural extracellular matrix hydrogel for inhibition of glioblastoma recurrence

期刊论文

Synergistic scale inhibition of polyaspartic acid composite with magnetic field

LIU Zhenfa, WANG Yanji, GAO Yuhua, ZHANG Lihui

期刊论文

Inhibition of NO emission by adding antioxidant mixture in

A. PRABU,R. B. ANAND

期刊论文

钨矿物原料NaOH分解过程中抑制杂质的研究

李洪桂,李运姣,孙培梅,刘茂盛

期刊论文

Absence of FHIT expression is associated with apoptosis inhibition in colorectal cancer

CAO Jie, LI Wanglin, XIA Jie, TANG Weibiao, WANG Hui, CHEN Xiwen, XIAO Huanqing, LI Yuyuan, CHEN Xiaoping, DU Hong, CHEN Shanming

期刊论文