EVALUATION OF ANTICLASTOGENIC POTENTIAL OF CINNAMOMUM CASSIA BARK EXTRACT AGAINST ARSENIC GENOTOXICITY BY USING MICRONUCLEUS ASSAY IN MUS MUSCULUS CAUDAL ERYTHROCYTES

Objective: The study was aimed to evaluate the anticlastogenic potential of ethanolic extract of Cinnamomum cassia against arsenic-induced genotoxicity.Methods: In the experiment, 30 animals were taken and divided into five groups and each group contains six animals. Group 1 was control and fed on tap water of Patna city while rest four (2, 3, 4, 5) groups were treated with 4 mg/kg body weight, per orally sodium arsenite for 8 weeks. Sodium arsenite pre-treated Groups 4 and 5 were followed by dose of 100 mg/kg body weight of 5% ethanolic solution of test plant bark extract for next 8 weeks (total duration of dosing 16 weeks). Caudal blood collected from each mouse by minor nick without their sacrifice and smeared blood was stained by double staining. Approximately, 2000 cells were scored by light microscopy to determine micronucleus (MN) frequency. The percentage of MN frequency was expressed in the terms of mean and standard deviation.Results: High index of MN frequency was observed in the Groups 2 and 3 while its frequency drastically reduced in Groups 4 and 5. The mean number of MN scored per 2000 cell were found to be 4.5, 23.5, 18.8, 10.5, and 9.66 in animal Groups 1, 2, 3, 4, 5,respectively.Conclusion: C. cassia may be effective drug in the area of preventive cancer or other kinds of diseases which lead to damage of genetic materials

Proteomic Study of Degenerative Protein Modifications in the Molecular Pathology of Neurodegeneration and Dementia

Dementia is a major public health burden, and the World Health Organization has identified this disorder as a major public health priority. There are limited treatment options due to poor understanding of key mechanism of dementia pathogenesis. Dementia has been regarded as a proteinopathy in which alterations of brain protein structure and function are the key features of the disorder. Proteinopathy can be triggered by degenerative protein modifications (DPMs), misfolding, aggregation, and deposition of the malformed proteins. Despite the clinical significance of alteration in protein abundances, DPMs, protein misfolding, and aggregation, the molecular mechanism that promotes these changes remains inadequately understood, mostly due to technical challenges. Proteomic is a powerful, sensitive, and advanced tool to study the progressive brain tissue damage that critically dysregulates key enzymes, accumulates modified proteins, and causes protein misfolding and aggregation, resulting in cognitive decline and dementia. The proteomic profiling of protein abundances and correlating DPMs with protein misfolding and aggregation have potential to elucidate underlying molecular mechanism of the disease. This chapter summarizes the recent proteomic developments for studying brain proteome, DPMs, and protein aggregation mechanism that may lead to dementia. We attempted to correlate DPMs and its impact on protein aggregation and deposition in brain tissues

Variability in the composition of extracellular polymeric substances from a full-scale aerobic granular sludge reactor treating urban wastewater

Within the framework of the circular economy, there is a need for waste management alternatives that promote the reuse of materials produced in wastewater treatment plants (WWTP). An interesting option is the recovery of extracellular substances from sludge. The variability of characteristics of potential recovered bioproducts has to be assessed in full scale operational settings. In this study, aerobic granular sludge (AGS) from a full-scale WWTP treating urban wastewater was regularly collected for 4 months to assess variability in extracellular polymeric substances (EPS) composition and in granular morphology. Variations in the EPS composition occurred with time. Proteins and humic substances were the main EPS components (329-494 and 259-316?mg/g VSS of AGS, respectively), with polysaccharides and DNA representing minor components. The application of an extra purification step after extraction to obtain a purer EPS led to a decrease in the yield of each EPS component, particularly pronounced for the polysaccharides. The final product had a rather constant composition for the monthly samples. The granules showed morphological stability throughout the sampling period and the yield of EPS was correlated to the size of the granules, higher when there was a higher content of small granules (Deq<150?µm) comparing to intermediate (150???Deq<1500?µm) or large granules (Deq?1500?µm). This is the first time that a potential valorization strategy for surplus AGS biomass is studied in a full-scale environment. Knowledge on yield and product homogeneity is important as these features are essential for downstream application of the recovered EPS.The authors wish to thank the company SIMTEJO for supplying the granules and influent and effluent characterization data. This work was financed by FCT under the project AGeNT - PTDC/BTA-BTA/31264/2017 (POCI-01-0145-FEDER-031264). We would like to thank the scientific collaboration of CBQF under the FCT project UID/Multi/50016/2019 and NORTE-08-5369-FSE-000007 and CEB under the FCT project UID/BIO/044697/2019 and BioTecNorte operation (NORTE-01-0145-FEDER-000004).info:eu-repo/semantics/publishedVersio

Thrombin and Plasmin Alter the Proteome of Neutrophil Extracellular Traps

Neutrophil extracellular traps (NETs) consist of a decondensed DNA scaffold decorated with neutrophil-derived proteins. The proteome of NETs, or “NETome,” has been largely elucidated in vitro. However, components such as plasma and extracellular matrix proteins may affect the NETome under physiological conditions. Here, using a reductionistic approach, we explored the effects of two proteases active during injury and wounding, human thrombin and plasmin, on the NETome. Using high-resolution mass spectrometry, we identified a total of 164 proteins, including those previously not described in NETs. The serine proteases, particularly thrombin, were also found to interact with DNA and bound to NETs in vitro. Among the most abundant proteins were those identified previously, including histones, neutrophil elastase, and antimicrobial proteins. We observed reduced histone (H2B, H3, and H4) and neutrophil elastase levels upon the addition of the two proteases. Analyses of NET-derived tryptic peptides identified subtle changes upon protease treatments. Our results provide evidence that exogenous proteases, present during wounding and inflammation, influence the NETome. Taken together, regulation of NETs and their proteins under different physiological conditions may affect their roles in infection, inflammation, and the host response

The biofilm matrix scaffold of Pseudomonas aeruginosa contains G-quadruplex extracellular DNA structures.

Extracellular DNA, or eDNA, is recognised as a critical biofilm component; however, it is not understood how it forms networked matrix structures. Here, we isolate eDNA from static-culture Pseudomonas aeruginosa biofilms using ionic liquids to preserve its biophysical signatures of fluid viscoelasticity and the temperature dependency of DNA transitions. We describe a loss of eDNA network structure as resulting from a change in nucleic acid conformation, and propose that its ability to form viscoelastic structures is key to its role in building biofilm matrices. Solid-state analysis of isolated eDNA, as a proxy for eDNA structure in biofilms, reveals non-canonical Hoogsteen base pairs, triads or tetrads involving thymine or uracil, and guanine, suggesting that the eDNA forms G-quadruplex structures. These are less abundant in chromosomal DNA and disappear when eDNA undergoes conformation transition. We verify the occurrence of G-quadruplex structures in the extracellular matrix of intact static and flow-cell biofilms of P. aeruginosa, as displayed by the matrix to G-quadruplex-specific antibody binding, and validate the loss of G-quadruplex structures in vivo to occur coincident with the disappearance of eDNA fibres. Given their stability, understanding how extracellular G-quadruplex structures form will elucidate how P. aeruginosa eDNA builds viscoelastic networks, which are a foundational biofilm property

Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks

settings Open AccessArticle Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks by Nancy Lan Guo 1,*,Tuang Yeow Poh 2,Sandra Pirela 3,Mariana T. Farcas 4,Sanjay H. Chotirmall 2,Wai Kin Tham 5,Sunil S. Adav 5,Qing Ye 1,Yongyue Wei 6,Sipeng Shen 2,David C. Christiani 2,Kee Woei Ng 3,7,8,Treye Thomas 9,Yong Qian 4 andPhilip Demokritou 3 1 West Virginia University Cancer Institute/School of Public Health, West Virginia University, Morgantown, WV 26506, USA 2 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore 3 Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA 4 Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA 5 Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore 6 Key Lab for Modern Toxicology, Department of Epidemiology and Biostatistics and Ministry of Education (MOE), School of Public Health, Nanjing Medical University, Nanjing 210029, China 7 School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore 8 Environmental Chemistry and Materials Centre, Nanyang Environment & Water Research Institute, Singapore 637141, Singapore 9 Office of Hazard Identification and Reduction, U.S. Consumer Product Safety Commission, Rockville, MD 20814, USA * Author to whom correspondence should be addressed. Int. J. Mol. Sci. 2019, 20(24), 6348; https://doi.org/10.3390/ijms20246348 Received: 2 December 2019 / Revised: 12 December 2019 / Accepted: 13 December 2019 / Published: 16 December 2019 (This article belongs to the Special Issue Advances in Nanostructured Materials between Pharmaceutics and Biomedicine) Download PDF Browse Figures Review Reports Cite This Paper Abstract Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. To the best of our knowledge, this is the first study systematically integrating in vivo, transcriptomics, metabolomics, and lipidomics to assess PEPs inhalation exposure-induced disease risks using a rat model