Tapan Chakrabarti

Beta Caryophyllene and Caryophyllene Oxide, Isolated from Aegle Marmelos, as the Potent Anti-inflammatory Agents against Lymphoma and Neuroblastoma Cells

Aegle marmelos (Indian Bael) is a tree which belongs to the family of Rutaceae. It holds a prominent position in both Indian medicine and Indian culture. We have screened various fractions of Aegle marmelos extracts for their anticancer properties using in vitro cell models. Gas chromatography-Mass spectrometry (GC-MS) was employed to analyze the biomolecules present in the Aegle marmelos extract. Jurkat and human neuroblastoma (IMR-32) cells were treated with different concentrations of the fractionated Aegle marmelos extracts. Flow cytometric analysis revealed that optimal concentration (50 µg/ml) of beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract can induce apoptosis in Jurkat cell line. cDNA expression profiling of pro-apoptotic and anti-apoptotic genes was carried out using real time PCR (RT-PCR). Down-regulation of anti-apoptotic genes (bcl-2, mdm2, cox2 and cmyb) and up-regulation of pro-apoptotic genes (bax, bak1, caspase-8, caspase-9 and ATM) in Jurkat and IMR-32 cells treated with the beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract revealed the insights of the downstream apoptotic mechanism. Furthermore, in-silico approach was employed to understand the upstream target involved in the induction of apoptosis by the beta caryophyllene and caryophyllene oxide fractions of Aegle marmelos extract. Herein, we report that beta caryophyllene and caryophyllene oxide isolated from Aegle marmelos can act as potent anti-inflammatory agents and modulators of a newly established therapeutic target, 15-lipoxygenase (15-LOX). Beta caryophyllene and caryophyllene oxide can induce apoptosis in lymphoma and neuroblastoma cells via modulation of 15-LOX (up-stream target) followed by the down-regulation of anti-apoptotic and up-regulation of pro-apoptotic genes.

Assessment of Traffic Noise on Highway Passing from Urban Agglomeration

Assessment of traffic noise pollution in developing countries is complex due to heterogeneity in traffic conditions like traffic volume, road width, honking, etc. To analyze the impact of such variables, a research study was carried out on a national highway passing from an urban agglomeration. Traffic volume and noise levels (L10, Lmin, Lmax, Leq and L90) were measured during morning and evening peak hours. Contribution of noise by individual vehicle was estimated using passenger car noise unit. Extent of noise pollution and impact of noisy vehicles were estimated using noise pollution level and traffic noise index, respectively. Noise levels were observed to be above the prescribed Indian and International standards. As per audio spectrum analysis of traffic noise, honking contributed an additional 3–4 dB(A) noise. Based on data analysis, a positive relationship was observed between noise levels and honking while negative correlation was observed between noise levels and road width. The study suggests that proper monitoring and analysis of traffic data is required for better planning of noise abatement measures.

Manganese exposure: Linking down-regulation of miRNA-7 and miRNA-433 with α-synuclein overexpression and risk of idiopathic Parkinson's disease

Manganese is an essential trace element however elevated environmental and occupational exposure to this element has been correlated with neurotoxicity symptoms clinically identical to idiopathic Parkinsons disease. In the present study we chronically exposed human neuroblastoma SH-SY5Y cells to manganese (100μM) and carried out expression profiling of miRNAs known to modulate neuronal differentiation and neurodegeneration. The miRNA PCR array results reveal alterations in expression levels of miRNAs, which have previously been associated with the regulation of synaptic transmission and apoptosis. The expressions of miR-7 and miR-433 significantly reduced upon manganese exposure. By in silico homology analysis we identified SNCA and FGF-20as targets of miR-7 and miR-433. We demonstrate an inverse correlation in expression levels where reduction in these two miRNAs causes increases in SNCA and FGF-20. Transient transfection of SH-SY5Y cells with miR-7 and miR-433 mimics resulted in down regulation of SNCA and FGF-20 mRNA levels. Our study is the first to uncover the potential link between manganese exposure, altered miRNA expression and parkinsonism: manganese exposure causes overexpression of SNCA and FGF-20 by diminishing miR-7 and miR-433 levels. These miRNAs may be considered critical for protection from manganese induced neurotoxic mechanism and hence as potential therapeutic targets.

Carbamazepine and oxcarbazepine removal in pharmaceutical wastewater treatment plant using a mass balance approach: A case study

The manufacturing of the antiepileptics, carbamazepine (CBZ) and oxcarbazepine (oxCBZ), results in generation of wastewater containing these micropollutants which exhibit toxicity even at trace levels. Therefore, we focused on monitoring their fate and removal in various units of a full-scale wastewater treatment plant (WWTP) using mass balance approach. An apparent CBZ removal of 50±3% was observed by conventional activated sludge process in the biological treatment unit, whereas oxCBZ still persisted after the biological treatment and showed negative mass balance. However, reverse osmosis resulted in 91% oxCBZ removal, whereas CBZ still continued to persist as a result of lower solubility of CBZ as compared to oxCBZ. Only 3% CBZ exhibited sorption onto the suspended solids and sludge, which was negligible for oxCBZ, thus demonstrating their tendency to remain in aqueous phase. Additionally, we attempted to understand the fundamental mechanism behind the removal of these pharmaceuticals and it was apparently the collective effect of sorption, mineralization, biotransformation, biodegradation, phototransformation/photodegradation, etc. Thus, the integrative data presented in the present study on productivity of these pharmaceuticals, their mass loading in influent and effluents allied with their removal efficiency will be significantly constructive in benchmarking the operational effectiveness through operational optimization and design improvement of the current conventional treatment plant.

Elevated levels of urinary 17-ketosteroids in central Indian children residing near sewage treatment plant and solid waste disposal plant: A preliminary study

ABSTRACT Urinary excretion of 17-ketosteroid (17-KS) was assessed in male pre-pubertal subjects aged (8–11 years; n = 90). Children living near sewage treatment plant and solid waste disposal plant (Group P) showed significantly higher levels of urinary 17-KS (Group P: 3.27 ± 1.63 µg/mL/CRE; p < 0.01) than children living in cleaner area (0.50 ± 0.53 µg/mL/CRE; Group C). Occurrence of urinary dibutyl phthalate in representative subjects of Group P (odds ratio: 9; p < 0.05; 95% of Confidence interval (CI) 1.93–72.99) was higher compared to Group C. Urinary concentrations of Cd (0.85 µg/g CRE ± 0.11), Mn (24.25 µg/g CRE ± 6.11) and Pb (12.39 µg/g CRE ± 2.86) in Group P were significantly (p < 0.01) higher than those found in Group C (Cd (0.28 µg/g CRE ± 0.03), Mn (13.33 µg/g CRE ± 3.20) and Pb (5.67 µg/g CRE ± 0.53)). Analyses of ambient air samples (PM10) in polluted area revealed major occurrence of phthalates, whereas derivatives of trifluoromethyl, dione, etc. were identified in PM2.5 fraction. Metal (Cd, Co, Mn and Pb) concentrations in ambient air (24 h, PM10) were higher in polluted area compared to cleaner area. We conclude that elevated levels of urinary 17-KS in Group P could be attributed to higher exposure of these subjects to Endocrine disrupting chemicals (EDCs) compared to Group C.

Application of cell-based assays for toxicity characterization of complex wastewater matrices: Possible applications in wastewater recycle and reuse

Exposure to pre-concentrated inlet or outlet STP wastewater extracts at different concentrations (0.001% to 1%) induced dose-dependent toxicity in MCF-7 cells, whereas drinking water extracts did not induce cytotoxicity in cells treated. GC-MS analysis revealed the occurrence of xenobiotic compounds (Benzene, Phthalate, etc.) in inlet/outlet wastewater extracts. Cells exposed to inlet/outlet extract showed elevated levels of reactive oxygen species (ROS: inlet: 186.58%, p<0.05, outlet, 147.8%, p<0.01) and loss of mitochondrial membrane potential (Δψm: inlet, 74.91%, p<0.01; outlet, 86.70%, p<0.05) compared to the control. These concentrations induced DNA damage (Tail length: inlet: 34.4%, p<0.05, outlet, 26.7%, p<0.05) in treated cells compared to the control (Tail length: 7.5%). Cell cycle analysis displayed drastic reduction in the G1 phase in treated cells (inlet, G1:45.0%; outlet, G1:58.3%) compared to the control (G1:67.3%). Treated cells showed 45.18% and 28.0% apoptosis compared to the control (1.2%). Drinking water extracts did not show any significant alterations with respect to ROS, Δψm, DNA damage, cell cycle and apoptosis compared to the control. Genes involved in cell cycle and apoptosis were found to be differentially expressed in cells exposed to inlet/outlet extracts. Herein, we propose cell-based toxicity assays to evaluate the efficacies of wastewater treatment and recycling processes.

GIS-Based Noise Simulation Open Source Software: N-GNOIS

Geographical information system (GIS)-based noise simulation software (N-GNOIS) has been developed to simulate the noise scenario due to point and mobile sources considering the impact of geographical features and meteorological parameters. These have been addressed in the software through attenuation modules of atmosphere, vegetation and barrier. N-GNOIS is a user friendly, platform-independent and open geospatial consortia (OGC) compliant software. It has been developed using open source technology (QGIS) and open source language (Python). N-GNOIS has unique features like cumulative impact of point and mobile sources, building structure and honking due to traffic. Honking is the most common phenomenon in developing countries and is frequently observed on any type of roads. N-GNOIS also helps in designing physical barrier and vegetation cover to check the propagation of noise and acts as a decision making tool for planning and management of noise component in environmental impact assessment (EIA) studies.