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Use of c. elegans as a 3R-compliant in vivo model for the chemoprevention of cisplatin-induced neurotoxicity

EXPERIMENTAL NEUROLOGY 2021年 341卷 113705页

作者： Wellenberg, Anna Weides, Lea Kurzke, Jennifer Hennecke, Till Bornhorst, Julia crone, Barbara Karst, Uwe Brinkmann, Vanessa Fritz, Gerhard Honnen, Sebastian Heinrich Heine Univ Fac Med Inst Toxicol Univ Str 1 D-40225 Dusseldorf Germany Univ Munster Inst Inorgan & Analyt Chem Corrensstr 30 D-48149 Munster Germany Univ Potsdam Inst Nutr Sci Arthur Scheunert Allee 114-116 D-14558 Nuthetal Germany Univ Wuppertal Fac Math & Nat Sci Food Chem Gaussstr 20 D-42119 Wuppertal Germany

Anticancer therapeutics can provoke severe side effects that impair the patient's quality of life. A frequent doselimiting side effect of platinum-based anticancer therapy is neurotoxicity. Its pathophysiology is poorly understood, and effective preventive or therapeutic measures are missing. Therefore, elucidation of the molecular mechanism of platinating drug-induced neurotoxicity and the development of preventive strategies is urgently needed. To this end, we aim to use c. elegans as a 3R-compliant in vivo model. The 3R principles were conceived for animal welfare in science concerning animal experiments, which should be replaced, reduced or refined. We can analytically demonstrate dose-dependent uptake of cisplatin (cisPt) in c. elegans, as well as genotoxic and cytotoxic effects based on DNA adduct formation (i.e., 1,2-GpG intrastrand crosslinks), induction of apoptosis, and developmental toxicity. Measuring the impairment of pharyngeal pumping as a marker of neurotoxicity, we found that especially cisPt reduces the pumping frequency at concentrations where basal and touch-provoked movement were not yet affected. cisPt causes glutathione (GSH) depletion and RNAi-mediated knockdown of the glutamatecysteine ligase GcS-1 aggravates the cisPt-induced inhibition of pharyngeal pumping. Moreover, N-acetylcysteine (NAc) mitigated cisPt-triggered toxicity, indicating that GSH depletion contributes to the cisPt-induced pharyngeal damage. In addition to NAc, amifostine (WR1065) also protected the pharynx of c. elegans from the toxic effects of cisPt. Measuring pharyngeal activity by the electrophysiological recording of neurotransmission in the pharynx, we confirmed that cisPt is neurotoxic in c. elegans and that NAc is neuroprotective in the nematode. The data support the hypothesis that monitoring the pharyngeal activity of c. elegans is a useful surrogate marker of cisPt-induced neurotoxicity. In addition, a low GSH pool reduces the resistance of neurons to cisPt treat

关键词： c elegans chemotherapy Neurotoxicity Platinating agents Neuroprotection 3-R principles Electrophysiological measurement

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chemical composition of crepis foetida L. and c. rubra L. volatile constituents and evaluation of the in vitro anti-inflammatory activity of salicylaldehyde rich volatile fraction

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BIOcHEMIcAL SYSTEMATIcS AND EcOLOGY 2021年 96卷

作者： Barda, c. Grafakou, M-E Kalpoutzakis, E. Heilmann, J. Skaltsa, H. Natl & Kapodistrian Univ Athens Sch Pharm Dept Pharmacognosy & Chem Nat Prod Athens 15771 Greece Univ Regensburg Fac Pharm & Chem Chair Pharmaceut Biol Regensburg Germany

The genus crepis L. (Asteraceae) comprises more than 200 currently recognized species. Several studies have been conducted on non-volatile phytochemicals of crepis spp., featuring mainly sesquiterpene lactones and phenolic derivatives. Nevertheless, no report has been made on assessing the volatile constituents of the genus. Therefore, the present study is the first report to the chemical composition of the volatile constituents of two odoriferous crepis spp., namely c. foetida L. and c. rubra L. Flowers and stems with leaves volatiles were analysed separately by gas chromatography coupled with mass spectrometry. In total, 37 volatile compounds were detected. Salicylaldehyde, carvacrol and aliphatic hydrocarbons are the main components of both c. foetida fractions, however c. rubra flowers are characterized by the abundance of beta-sitosterol and eicosanoic acid, while the stems-leaves volatiles revealed to be more complex with hydrocarbons as main constituents. In addition, we investigated the salicylaldehyde rich volatile fraction for its in vitro activity on TNF-alpha induced IcAM-1 expression.

关键词： crepis c foetida c rubra Gc-MS Volatile constituents

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A DNA Damage-Repair Dynamic Model for HRS/IRR Effects of c.elegans Induced by Neutron Irradiation

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DOSE-RESPONSE 2021年第1期19卷

作者： Feng, Guangyan Zhang, Lianxin Yang, Zhanguo Zhang, Yong Zhang, Siwei Li, Taosheng Xu, Zhao Anhui Univ Inst Phys Sci & Informat Technol Hefei Anhui Peoples R China Chinese Acad Sci Hefei Inst Phys Sci Hefei Anhui Peoples R China Univ Sci & Technol China Hefei Anhui Peoples R China

Neutron irradiation which could trigger severe biological effects, is being applied in nuclear plants, radiotherapy, and aerospace gradually. Low dose hyper-radiosensitivity response of low Linear Energy Transfer (LET) irradiation on the cell survival has become a matter of great interest since its discovery, but a few research have been done on this response induced by neutron irradiation. To investigate this response induced by neutron irradiation, caenorhabditis elegans (c. elegans) was irradiated by neutron irradiation. The surviving fraction of c. elegans on the 12th day after irradiation was analyzed, which showed a hyper-radiosensitive response at low doses and followed by an increase in survival fraction at slightly higher doses. The finding of this work that neutron irradiation decreased the surviving fraction in a non-dose-dependent manner was different from previous low-LET irradiation studies. To understand the experimental results, a DNA damage-repair model was introduced. By comparing experimental results with theoretical analyses, we suggest that the low dose hyper-radiosensitivity response of neutron irradiation may possible related to different radiation types and DNA damage recognition proteins and immune system of c. elegans.

关键词： hyper-radiosensitivity neutron c elegans surviving-fraction damage-repair model

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Phenolic acid metabolites of polyphenols act as inductors for hormesis in c. elegans

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MEcHANISMS OF AGEING AND DEVELOPMENT 2021年 198卷 111518页

作者： Dilberger, Benjamin Weppler, Selina Eckert, Gunter P. Justus Liebig Univ Giessen Biomed Res Ctr Seltersberg BFS Inst Nutr Sci Lab Nutr Prevent & Therapy Schubertstr 81 D-35392 Giessen Germany

Introduction: Aging represents a major risk factors for metabolic diseases, such as diabetes, obesity, or neurodegeneration. Polyphenols and their metabolites, especially simple phenolic acids, gained growing attention as a preventive strategy against age-related, non-communicable diseases, due to their hormetic potential. Using caenorhabditis elegans (c. elegans) we investigate the effect of protocatechuic, gallic, and vanillic acid on mitochondrial function, health parameters, and the induction of potential hormetic pathways. Methods: Lifespan, heat-stress resistance and chemotaxis of c. elegans strain P X 627, a specific model for aging, were assessed in 2-day and 10-day old nematodes. Mitochondrial membrane potential (Delta Psi m) and ATP generation were measured. mRNA expression levels of longevity and energy metabolism-related genes were determined using qRT-PcR. Results: All phenolic acids were able to significantly increase the nematodes lifespan, heat-stress resistance and chemotaxis at micromolar concentrations. While Delta Psi m was only affected by age, vanillic acid (VA) significantly decreased ATP concentrations in aged nematodes. Longevity pathways, were activated by all phenolic acids, while VA also induced glycolytic activity and response to cold. conclusion: While life- and health span parameters are positively affected by the investigated phenolic acids, the concentrations applied were unable to affect mitochondrial performance. Therefore we suggest a hormetic mode of action, especially by activation of the sirtuin-pathway.

关键词： c elegans PX627 Polyphenols Metabolites Hormesis Mitochondria

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Distributions of Ion Density Irregularities and Their Gradients Inside Low-Latitude Ionospheric Plasma Bubbles Based on c/NOFS Planar Langmuir Probe Data

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SPAcE WEATHER-THE INTERNATIONAL JOURNAL OF RESEARcH AND APPLIcATIONS 2021年第3期19卷

作者： costa, Emanoel Roddy, Patrick A. Ballenthin, John O. Pontificia Univ Catolica Rio de Janeiro PUC Rio Ctr Estudos Telecomunicacoes CETUC Rio De Janeiro Brazil Air Force Res Lab Space Vehicles Directorate Kirtland Air Rorce Base NM USA

Data from the planar Langmuir probe onboard the communication/Navigation Outage Forecasting System has been processed, with focus on the: (1) identification of Equatorial Plasma Bubbles located within the eclipse sections of the satellite orbits;(2) subdivision of each Equatorial Plasma Bubble into three sections (West Wall, center, and East Wall);and (3) statistical analyses of the standard deviations and gradients of ion density data for each section. The statistical distributions resulted from the application of the above processing to structures identified during the years October 1, 2008 to September 30, 2009 (solar minimum conditions) and June 5, 2012 to June 4, 2013 (close to maximum conditions of solar cycle 24). The statistical distributions have also been classified considering all longitudes or three 60 degrees longitude sectors in South America, Africa, India-Asia, as well as all altitudes of the c/NOFS satellite or the limited range from 650 to 800 km. It will be shown that all the parameters (Equatorial Plasma Bubble sections, solar activity, longitude sector, and altitude range) affect the resulting statistical distributions. Additionally, the probability density functions (pdfs) of ion density gradients for the EPB West Walls, centers, and East Walls and the South American longitude sector, detected during 2012 and estimated with different resolutions will be compared. While the pdfs based on 1-Hz low-resolution data (sampling large-scale structures) display east-west asymmetries, those based on the original 512-Hz high-resolution data (sampling small-scale structures), created by secondary plasma instabilities, are essentially symmetric around the reference 0 mm/km gradient.

关键词： c NOFS PLP Equatorial Plasma Bubbles standard deviations and gradients of ion density data

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Toxocara DNA amplification in serum and tissue samples in BALB/c mice

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MOLEcULAR AND BIOcHEMIcAL PARASITOLOGY 2021年 246卷 111429页

作者： Rodrigues e Fonseca, Gabriela de Melo, Gessica Baptista de Paula, Fabiana Martins Malta, Fernanda Mello Borges Gryschek, Ronaldo cesar Zevallos Lescano, Susana Angelica Univ Sao Paulo Lab Invest Med Imunopatol Esquistossomose LIM 06 Hosp Clin Fac Med Av Dr Eneas Carvalho Aguiar 470 BR-05403000 Sao Paulo SP Brazil Univ Sao Paulo Inst Med Trop Fac Med Ave Dr Eneas Carvalho Aguiar 470 BR-05403000 Sao Paulo SP Brazil Univ Sao Paulo Lab Gastroenterol Clin Expt LIM 07 Hosp Clin Fac Med Av Dr Eneas Carvalho Aguiar 470 BR-05403000 Sao Paulo SP Brazil Hosp Israelita Albert Einstein Av Albert Einstein 627-701 BR-05652900 Sao Paulo SP Brazil

Toxocariasis is still a neglected parasitic disease worldwide and much about its biology and diagnosis has yet to be understood. The migration of third stage larvae via bloodstream suggests a potential use of molecular tools in diagnosis as well to deepen the knowledge about its migration behaviors. conventional PcR was applied in serum and tissue samples from BALB/c mice infected with 5 and 500 embryonated eggs. Blood samples were collected at 15, 30, 60, 90 and 120 days post-infection. Organs were excised at 170 days post infection. There was no DNA amplification in serum samples in any group or day post-infection;contrarily, tissue samples showed DNA amplification. These results also support a continuous larval migration after and/or simultaneously with the neurotropic-myotropic phase. Thus, molecular tools might be useful as a differential diagnosis method, but do not replace immunodiagnostics techniques.

关键词： PcR Toxocara Migration BALB c

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Remarkable enhancement of visible light driven photocatalytic performance of TiO2 by simultaneously doping with c, N, and S

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cHEMIcAL PHYSIcS 2021年 545卷

作者： Thi Thanh Thuy Le Dinh Trinh Tran Thi Huong Danh Qui Nhon Univ Fac Sci Dept Chem 170 Duong Vuong Str Qui Nhon Vietnam Vietnam Natl Univ Univ Sci VNU Key Lab Adv Mat Green Growth 19 Le Thanh Tong Str Hanoi Vietnam

TiO2 modified with c, N and S were produced by hydrothermal treatment and sol-gel method using thiourea as the precursor. The characteristic of the materials were examined by means of XPS, XRD, UV-VIS, SEM, EDX, and FT-IR. The results showed that c, N and S were successfully doped into TiO2 lattice, leading to a decline in recombination rate of electrons/holes, and a shift of absorption edge of TiO2 to visible light region. The photocatalytic performance of as synthesized catalysts were evaluated via the degradation of rhodamine B under visible light irradiation. N,c,S-TiO2 demonstrated the highest photocatalytic efficiency and a perspective recyclable potential. The optimal photocatalyst dose was 1.8 g/L, and the best RhB initial concentration was 20 mg/ L. At the optimal conditions, almost 100% of RhB were removed after 1.5 h. The photodegradation of RhB followed the seudo first-order kinetics, with the maximum rate constant of 0.0410 min(-1).

关键词： Titanium dioxide c N S tri-doping Visible light Photocatalytic enhancement Rhodamine B Kinetics

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Interleukin-6 versus c-reactive Protein as Markers for Early Detection of Bacteremia in Febrile Neutropenia in Pediatric Population

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Indian Journal of Medical and Paediatric Oncology 2021年第5期41卷 702-706页

作者： Manasi Gupta Pushpa G Kini Y Ramesh Bhat Shrikiran Aroor Department of Paediatrics Kasturba Medical College and Hospital Manipal Academy of Higher Education Manipal Karnataka India

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Spleen proteome profiling of dairy goats infected with c. pseudotuberculosis by TMT-based quantitative proteomics approach

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JOURNAL OF PROTEOMIcS 2021年 248卷 104352页

作者： Fu, Mingzhe Yan, Yuchao Su, Hong Wang, Jingjing Shi, Xiaojie Zhou, Hongchao Zhang, Qi Xu, Xingang Northwest A&F Univ Coll Vet Med Yangling 712100 Shaanxi Peoples R China

corynebacterium pseudotuberculosis (***) is a zoonotic pathogen that can cause cheese lymphadenitis in goats. In order to obtain detailed information about the pathogenesis and host immune response of goats infected with ***, we used tandem mass tag (TMT)-labeling proteomic analysis to detect differentially expressed proteins (DEPs) in dairy goats infected with ***, and confirmed the altered proteins with western blot. A total of 6611 trusted proteins were identified, and 126 proteins were differentially abundant. Gene ontology (GO) analysis showed that all DEPs were annotated as biological processes, cell composition, and molecular functions. Biological processes mainly involve acute inflammation and immune response;cell components mainly involve extracellular areas and high-density lipoprotein particles;molecular functions are mainly antigen binding, ferric iron binding, and iron ion binding. KEGG analysis showed that a total of 102 pathways were significantly enriched, mainly lysosomes, phagosomes, and mineral absorption pathways. Our findings provided the relevant knowledge of spleen protein levels in goats infected with c. pseudotuberculosis and revealed the complex molecular pathways and immune response mechanisms in the process of *** infection. Significance: *** is the most fatal infectious disease in dairy goats, causing huge economic losses. However, the molecular pathways and immune response mechanisms of *** infection in goats remain unclear. Therefore, we conducted a comparative quantitative proteomics study on dairy goats infected with ***. The results provide a basis for better understanding the complexity of *** infection, reveal the complex molecular pathways and immune response mechanisms in *** infection, and provide some clues for identifying potential therapeutic targets. This is the first repor

关键词： c pseudotuberculosis Tandem mass tag (TMT) Proteomics Dairy goats

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Wear analysis of Al7075 alloyed with nano B 4 c: A taguchi approach

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Materials Today: Proceedings 2021年 47卷 2603-2607页

作者： T.H. Manjunatha Yadavalli Basavaraj V. Venkata Ramana Ballari Institute of Technology and Management Allipura Ballari 583104 India

The paper discusses about a novel combination of Aluminium 7075 reinforced with Boron carbide (B4c) in nano form in terms of wear behavior. This type of composites are popular now a day's addressing various needs of industry especially where the weight, mechanical and wear properties of the alloy have a significant effect on end application. The present investigational work involves base metal Aluminium 7075 reinforced with B4c in nano form in various percentages by weight (3 to 12%). The specimens were prepared by stir casting process as per ASTM standards and were tested for their behavioral aspects towards wear using pin on disc. The taguchi approach was applied to optimize the process parameters for the case. The process has four factors, four levels considering, composition of nano B4c as 3%,6%, 9% and 12%, load variations in steps are 10, 20, 30 and 40 N, speeds selected are 100, 200, 300, and 400 rpm respectively and sliding distances preferred are 500,1000,1500 and 2000 m to study the effects on wear. Post experimentation analysis established that the presence of nano B4c particles has shown considerable reduction in wear with the samples.

关键词： Taguchi technique Wear Aluminium 7075 Nano B 4 c

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