Estimated exposure to microplastics through national and local brands of bottled water in Central India.

Microplastics (MPs) are ubiquitous pollutants that affect various environmental matrices, including air, water, soil, food, and beverages. In India, there is limited research on microplastics in bottled drinking water, which is a significant route of MP exposure to the human body. To date, the data on the occurrence of MPs in national and local bottled water brands have not been studied and compared. Therefore, the current study focuses on the contamination of MPs in bottled water from different national and local brands procured from the market of Nagpur, India. The MPs were observed in all the analyzed samples. It was observed that the local bottled water showed higher MP contamination compared to national bottled water, with MP concentrations of 212 ± 100 MPs/L and 72 ± 36 MPs/L, respectively. The MPs were identified and characterized using microscopic and attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR) analysis, revealing that the dominant MP particles were fragments (71%), followed by fibers (23%), and others (6%). Among the observed particles, 50% of particles were black colored, followed by transparent (16%), red (13%), orange (8%), green (3%), blue (5%), and yellow (5%). The predominant polymer types were polyethylene (PE) and polyethylene terephthalate (PET). Overall, the pollution load indices suggested a moderate level of contamination in bottled water samples. Furthermore, the estimated annual human exposure to MPs was calculated as 5186 ± 3751 p/kg-bw/year for children and 1482 ± 1072 p/kg-bw/year for adults, making it a significant route of human exposure to MPs.

Screening, identification, and characterization of lipase-producing halotolerant Bacillus altitudinis Ant19 from Antarctic soil.

Potent lipase-producing and halotolerant Bacillus altitudinis Ant19 strain was screened and isolated from Antarctic soil. The isolate showed broad-range lipase activity against different lipid substrates. Presence of lipase activity was confirmed by PCR amplification and sequencing of the lipase gene from Ant19. The study attempted to establish the use of crude extracellular lipase extract as cheap alternative to purified enzyme by characterizing the crude lipase activity and testing it in certain practical applications. Crude lipase extract from Ant19 showed high stability at 5-28 â„ƒ (> 97%), while lipase activity was noted in a wide temperature range of 20-60 â„ƒ (> 69%), with optimum activity at 40 â„ƒ (117.6%). The optimum lipolytic activity was noted at pH 8 with good activity and stability in alkaline conditions (pH 7-10). Moreover, the lipase activity was substantially stable in various solvents, commercial detergents, and surfactants. It retained 97.4% activity in 1% solution of commercial Nirma detergent. Besides, it was non-regiospecific, and active against substrates having different fatty acid chain lengths with preference for shorter chain length. Further, the crude lipase enhanced the oil stain removal efficiency of commercial detergent from 52 to 77.9%, while 66% oil stain was removed using crude lipase alone. Immobilization process improved the storage stability of crude lipase for 90 days. In our knowledge, it is the first study on characterization of lipase activity from B. altitudinis, which has promising applications in various fields.

Characterization and removal of microplastics in a sewage treatment plant from urban Nagpur, India.

Sewage treatment plant (STP) acts as a potential source of microplastic contamination in the environment. The presence of microplastics in the sewage treatment plant is reported over the globe in varying concentrations. Hence, the current study is intended to evaluate the presence and abundance of microplastics occurring in sewage treatment plants in India. The samples were processed through digestion and density separation, followed by microscopic and polymer identification through Fourier transform infrared spectroscopy. Also, different wastewater parameters were studied to analyze their influence. High microplastic concentrations were detected in the influent (1860 ± 265 MPs/L), which reduced by > 90%, to around 148 ± 51 MPs/L in the effluent. The concentration of microplastics in sewage sludge was 830 MPs/kg. The prominent plastic types identified include low-density polyethylene, polypropylene, polyurethane, polyvinyl chloride, and rayon. The smaller particles prevail in the effluent, releasing around 30 billion particles per day to the environment. This suggests that the current STP is efficient in removing the majority of the particles, but considerations are needed to avoid the ecological risks associated.

Mitochondrial dysfunctions elicited by solid waste leachates provide insights into mechanisms of leachates induced cell death and pathophysiological disorders.

Emissions (mainly leachates and landfill gases) from solid waste facilities are laden with mixtures of dangerous xenobiotics implicated with significant increase in various pathophysiological disorders including cancer, and eventual mortality of exposed wildlife and humans. However, the molecular mechanisms of solid waste leachates induce pathophysiological disorders and cell death are still largely unknown. Although, evolving evidence implicated generation of reactive oxygen species and oxidative stress as the possible mechanism. Recent scientific reports are linking reactive oxygen species and mitochondrial dysfunctions as the player mechanism in pathophysiological disorder and apoptosis induced by xenobiotics in solid waste leachates. This systematic review presents an explicit discussion of recent scientific findings on the structural and functional alterations in mitochondria induced by solid waste leachates as the molecular mechanisms plausibly responsible for the pathophysiological disorders, cancer and cell death reported in landfill toxicology and epidemiological studies. This review aims to increase scientific understanding on solid waste leachate induced mitochondria dysfunctions as the key player in molecular mechanisms of solid waste induced toxicity. The findings in this review were mainly from using primary cells, cell lines, Drosophila and fish. Whether the findings will similarly be observed in mammalian test systems in vivo and particularly in exposed humans, remained to be investigated. Improvement in technological advancements, enforcement of legislation and regulations, and creation of sophisticated health surveillance against exposure to solid waste leachates, will expectedly mitigate human exposure to solid waste emissions and contamination of the environment.

Can the Indian national ambient air quality standard protect against the hazardous constituents of PM2.5?

Globally, exposure to ambient fine particulate matter (PM2.5) pollution claims ∼9 million lives, yearly, and a quarter of this deaths occurs in India. Regulation of PM2.5 pollution in India is based on compliance with its National Ambient Air Quality Standard (NAAQS) of 40 µg/m3, which is eight times the revised global air quality guideline (AQG) of 5 µg/m3. But, whether the NAAQS provides adequate protection against the hazardous components in PM2.5 is still not clear. Here, we examined the risk to health associated with exposure to PM2.5-bound polychlorinated biphenyls (PCB), heavy metals and polycyclic aromatic hydrocarbons (PAHs) in an Indian district averaging below the NAAQS. The annual average concentrations of PM2.5 mass, Σ28PCB and Σ13PAHs were 34 ± 17 µg/m3, 21 ± 12 ng/m3 and 458 ± 246 ng/m3, respectively. Concentrations of As, Cr, Mn and Ni in PM2.5 surpassed the screening levels for residential air. Substantial level of risks to health were associated with exposure to dioxin-like PCBs (Σ12dlPCB), PAHs, As, Cr and Ni. The hazard index or lifetime cancer risk were 240, or 9 cases per 1000 population, respectively. The estimated risks to health through exposure to hazardous components, except Ni, were greatest in rural areas, having a lower average PM2.5 concentration, than urban or peri-urban areas, suggesting higher toxicity potential of rural combustion sources. The large disparity between the estimated risk values and the acceptable risk level suggests that it would take a more stringent standard, such as the global AQG, to protect vulnerable populations in India from hazardous components in PM2.5.

Landfill soil leachates from Nigeria and India induced DNA damage and alterations in genes associated with apoptosis in Jurkat cell.

Landfill soil leachates, containing myriad of xenobiotics, increase genotoxic and cytotoxic stress-induced cell death. However, the underlying mechanism involved in the elimination of the damaged cells is yet to be fully elucidated. This study investigated the apoptotic processes induced in lymphoma (Jurkat) cells by landfill soil leachates from Olusosun (OSL, Nigeria) and Nagpur (NPL, India). Jurkat was incubated with sub-lethal concentrations of OSL and NPL for 24 h and analyzed for DNA fragmentation and apoptosis using agarose gel electrophoresis and Hoechst 33258-PI staining, respectively. Complementary DNA expression profiling of some pro-apoptotic and anti-apoptotic genes regulating apoptosis was also analyzed using real-time PCR (RT-PCR) method. Agarose gel electrophoresis revealed DNA fragmentations in OSL and NPL-treated cells. Hoecsht-33258 - Propidium Iodide (PI) based apoptotic analysis confirmed apoptotic cell death in exposed Jurkat. RT-PCR analysis revealed different fold changes in the pro- and anti-apoptotic genes in OSL and NPL-treated Jurkat. There was significant increase in fold change of the up-regulated genes; apoptosis inducing factor mitochondrion-associated 2 (AIFM2), Fas-associated death domain (FADD), Caspase-2, Caspase-6, BH3 interacting domain death agonist (BID), tumor suppressor (p53), and BCL2 associated agonist of cell death (BAD) and down-regulation of apoptosis inhibitor 5 (API5). Results suggest that OSL and NPL elicited genotoxic stress-related apoptosis in Jurkat. The dysregulation in the expression of genes involved in apoptotic processes in wildlife and human exposed to landfill emissions may increase aetiology of various pathological diseases including cancer.

Assessment of occupational exposure to diesel particulate matter through evaluation of 1-nitropyrene and 1-aminopyrene in surface coal miners, India.

DPM (diesel particulate matter) is ubiquitously present in the mining environment and is known for mutagenicity and carcinogenicity to humans. However, its health effects in surface coal mines are not well studied, particularly in India. In this study, DPM exposure and corresponding exposure biomarkers were investigated in four different surface coal mines in Central India. To document and evaluate the DPM exposure in surface coal miners, we characterized 1-NP (1-nitropyrene) in the mining environment as surrogate for DPM using Sioutas Cascade Impactor. Exposure biomarkers were analyzed by collecting post work shift (8-h work shift) urine samples and determining the concentrations of 1-aminopyrene (1-AP) as a metabolite of 1-NP and 8-hydroxydeoxyguanosine (8OHdG) as DNA damage marker. We observed high concentration of 1-NP (7.13-52.46 ng/m3) in all the mines compared with the earlier reported values. The average creatinine corrected 1-AP and 8OHdG levels ranged 0.07-0.43 [Formula: see text]g/g and 32.47-64.16 [Formula: see text]g/g, respectively, in different mines. We found 1-AP in majority of the mine workers' urine (55.53%) and its level was higher than that reported for general environmental exposure in earlier studies. Thus, the study finding indicates occupational exposure to DPM in all the four mines. However, the association between 1-NP level and exposure biomarkers (1-AP and 8OHdG) was inconsistent, which may be due to individual physiological variations. The data on exposure levels in this study will help to understand the epidemiological risk assessment of DPM in surface coal miners. Further biomonitoring and cohort study are needed to exactly quantify the occupational health impacts caused by DPM among coal miners.

Environmental prevalence, fate, impacts, and mitigation of microplastics-a critical review on present understanding and future research scope.

Microplastics are considered to be ubiquitous and widespread emerging contaminants. They are persistent in the nature and pose considerable harm to the environment. Their omnipresence is documented in almost all aquatic habitats, several atmospheric and terrestrial environments, and also in human consumables. The objective of this review is to provide an overview of the environmental prevalence of the microplastics in all environmental compartments, and their possible adverse impacts. It also presents review of the studies conducted in India and the epitome of potential mitigation measures. The need and direction of future research are highlighted. The review will help in determining the exposure levels, environmental consequences, and risk estimations, and will guide the researchers and policymakers.

Burn to kill: Wood ash a silent killer in Africa.

Aside the emissions, burning of wood in traditional cookstoves (TCs) also generates substantial amount of ash containing hazardous pollutants such as polycyclic aromatic hydrocarbons (PAHs) and toxic metals. But, their concentrations in the ash, particularly in Africa where over 70% of the population utilize TCs, remain unknown. Here, we determined concentrations of sixteen PAHs and eleven heavy metals in ashes from twelve different African TCs, comprising six three-stone fires (TSFs) and six built-in-place cookstoves (BIPCs), burning common African wood species under real world situation. For each TC, ash samples were collected for six consecutive days (Monday-Saturday), and a total of seventy-two daily samples were collected from January-June 2019. Ash yields were measured gravimetrically, and concentrations of the pollutants were determined following standard analytical protocols. The results were used alongside secondary data (annual fuelwood consumption, African fuelwood densities, population proportion using fuelwood and surface human population density) to estimate annual tonnage, exposure potential and risk to health in Africa, using Monte Carlo simulation technique. The ash yields from all TCs studied exceeded 1% on dry weight basis, indicating that ash is a major waste by-product of wood combustion in TCs. TSFs produced more ash (5.7 ± 0.7%) than BIPCs (3.4 ± 1.0%). Concentrations of As, Cd, Hg and Pb in ashes were significantly higher (α = 0.05) for TSFs than BIPCs. In contrast, concentrations of PAHs were higher in ashes from BIPCs than TSFs. Assuming ash consumption rates range from 250 to 500 mg/day for young children weighing 10 to 30 kg, the upper dose (µg/kg-day) of Pb (0.2-3.9) or Σ16PAHs (0.02-0.34), for instance, surpasses the 0.3 µg/kg-day of Pb or PAH recognized as causing adverse effects in children, indicating a concern. The top five countries with the highest annual tonnage or exposure potential to toxic pollutants are Nigeria>Ethiopia>DR-Congo>Tanzania>Uganda, or Rwanda>Burundi>Uganda>Nigeria>Guinea-Bissau, respectively.

Remediation of different nitroaromatic pollutants by a promising agent of Cupriavidus sp. strain a3.

Nitrobenzene, nitrotoluenes and nitrobenzoic acid are toxic and mutagenic. Their removal from the environment is necessary to avoid health and environmental damage. In this study, Cupriavidus strain a3 was found to utilize 2-nitrotoluene (2NT), 3-nitrotoluene (3NT), 4-nitrotoluene (4NT), nitrobenzene (NB) and 2-nitrobenzoic acid (2NBA) as carbon and nitrogen source, resulting in their detoxification. The metabolism involved reductive transformation of nitroaromatics to the corresponding amines followed by cleavage of amino group to release ammonia. Cell free extract showed nitroreductase activity in the range of 310-389 units/mg. NB was reduced to form benzamine and 4-aminophenol, 2NT was reduced to 2-aminotoluene, whereas 2NBA was reduced to form 2-aminobenzoic acid. Similarly, 3NT was metabolized to 3-aminotoluene and 2-amino-4-methylphenol, while 4NT was reduced to 4-nitrosotoluene and 4-aminotoluene. Cytotoxicity and apoptosis assays using Jurkat cell line, and Ames test were used to evaluate the detoxification of nitroaromatics during biodegradation. Biodegradation with Cupriavidus resulted in 2.6-11 fold increase in cell viability, 1.3-2.3 fold reduction in apoptosis, 1.6-55 fold reduction in caspase-3 activation, and complete disappearance of mutagenic activity. In soil microcosm, bioaugmentation with Cupriavidus resulted in 16-59% degradation of various nitroaromatics, as against <14% degradation without bioaugmentation. Thus, the present study reflects promising capability of Cupriavidus strain a3 in degradation and detoxification of multiple nitroaromatics.

Environmental persistence, hazard, and mitigation challenges of nitroaromatic compounds.

Nitroaromatic compounds (NACs) are extensively used in different industries and are synthesized in large quantity due to their heavy demand worldwide. The broad use of NACs poses a serious pollution threat. The treatment processes used for the removal of NACs are not effective and sustainable, leading to their release into the environment. The nitro group attached to benzene ring makes the compounds recalcitrant due to which they persist in the environment. Being hazardous to human as well as other living organisms, NACs are listed in the USEPA's priority pollutant group. This review provides updated information on the sources of NACs, prevalence in different environmental matrices, and recent developments in methods of their detection, with emphasis on current trends as well as future prospects. The harmful effects of NACs due to exposure through different routes are also highlighted. Further, the technologies reported for the treatment of NACs, including physico-chemical and biological methods, and the challenges faced for their effective implementation are discussed. Thus, the review discusses relevant issues in detail making suitable recommendations, which can be helpful in guiding further research in this subject.

Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.).

OBJECTIVE: Garden cress (Lepidium sativum L.) is an important herb in traditional medicine used to improve production of breast milk in women and semen in men. In the present research the authors evaluated its ability to destroy leukemic cancer (Jurkat E6-1) cells, using the alkaloid extract of this plant. METHODS: Constituents of the alkaloid extract were analyzed by gas chromatography-mass spectrometry (GC-MS) and their cytotoxicity in leukemic cancer cells and healthy peripheral blood mononuclear cells (PBMCs) was assessed. Cell death via apoptosis was confirmed by DNA laddering, caspase-3 activity, annexin V-fluorescein isothiocyanate and mitochondrial toxicity assays. The specific course of gene activation in treated cells was determined through quantitative polymerase chain reaction (qPCR). RESULTS: GC-MS analysis identified six alkaloids and proto-alkaloids, namely, benzyl isothiocyanate (1), 2-ethoxy-4H-3,1-benzoxazin-4-one (2), (4R)-2-(2-aminophenyl)-4-phenyloxazoline (3), 5-acetyl-1,2-dihydro-6-methyl-2-oxo-4-phenyl-3-pyridinecarbonitrile (4), benzo[b][1,8]-naphthyridin-5(10H)-one,2,4,7-trimethyl (5) and 1,4-diaminoanthraquinone (6), in the alkaloid extract of L. sativum. Of these, compound 1 was previously identified in the seeds of L. sativum. Exposure to the alkaloid extract caused death of Jurkat E6-1 cells, with median lethal concentration (LC50) of 75.25 µg/mL. However, the alkaloid extract also showed a nontoxic and proliferative (1.6-fold) effect in healthy PBMCs. Further experiments performed with Jurkat cells at LC50 and sub-LC50 doses demonstrated DNA fragmentation, activation of caspase-3 and time-dependant phosphatidylserine translocation (apoptosis) from inner to outer cell membranes. Cell toxicity and assessment of adenosine triphosphate level, together with using qPCR to evaluate expression profile of major apoptosis genes, revealed that apoptosis may be induced by disruption in the mitochondrial outer membrane potential, through activation of extrinsic and intrinsic apoptosis pathways in Jurkat cells. CONCLUSION: The ability of the alkaloid extract of L. sativum seeds to induce apoptosis indicates a potential pharmacological use in cancer chemotherapy. The separation of individual active compounds and further in-depth exploration of the molecular mechanism of apoptosis may lead to novel chemotherapeutic compounds in our future antineoplastic research.

Optimization and scale up of itaconic acid production from potato starch waste in stirred tank bioreactor.

Present study used Aspergillus terreus strain C1 isolated from mangrove soil for itaconic acid (IA) production from potato starch waste. Fermentation parameters were optimized by classical one factor approach and statistical experimental designs, such as Plackett-Burman and response surface designs. Anionic deionization of potato waste was found to be a very effective, economic, and easy way of improving IA production. The increase in IA production by deionization was found to correlate with removal of phosphate. In our knowledge, this is the first report on application of deionization of potato waste to enhance IA production. Other parameters like inoculum development conditions, pH, presence of peptone and certain salts in the medium also significantly affected IA production. IA production by strain C1 increased 143-fold during optimization when compared with the starting condition. The optimized IA level (35.75 g/L) was very close to the maximum production predicted by RSM (38.88 g/L). Bench scale production of IA was further optimized in 3-L stirred tank reactor by varying parameters like agitation and aeration rate. The maximum IA production of 29.69 g/L was obtained under the agitation speed of 200 rpm and aeration rate of 0.25 vvm. To the best of our knowledge, it is the first report on IA production from potato starch waste at bioreactor level. © 2019 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2774, 2019.

Role of fluoride induced epigenetic alterations in the development of skeletal fluorosis.

Fluoride is an essential trace element required for proper bone and tooth development. Systemic high exposure to fluoride through environmental exposure (drinking water and food) may result in toxicity causing a disorder called fluorosis. In the present study, we investigated the alteration in DNA methylation profile with chronic exposure (30 days) to fluoride (8 mg/l) and its relevance in the development of fluorosis. Whole genome bisulfite sequencing (WGBS) was carried out in human osteosarcoma cells (HOS) exposed to fluoride. Whole genome bisulfite sequencing (WGBS) and functional annotation of differentially methylated genes indicate alterations in methylation status of genes involved in biological processes associated with bone development pathways. Combined analysis of promoter DNA hyper methylation, STRING: functional protein association networks and gene expression analysis revealed epigenetic alterations in BMP1, METAP2, MMP11 and BACH1 genes, which plays a role in the extracellular matrix disassembly, collagen catabolic/organization process, skeletal morphogenesis/development, ossification and osteoblast development. The present study shows that fluoride causes promoter DNA hypermethylation in BMP1, METAP2, MMP11 and BACH1 genes with subsequent down-regulation in their expression level (RNA level). The results implies that fluoride induced DNA hypermethylation of these genes may hamper extracellular matrix deposition, cartilage formation, angiogenesis, vascular system development and porosity of bone, thus promote skeletal fluorosis.

Molecular mechanism of apoptosis induction in Jurkat E6-1 cells by Tribulus terrestris alkaloids extract.

The present study demonstrates apoptosis-inducing potential and mechanism of action of Tribulus terristris alkaloid extract in Jurkat E6-1 cancer cell line. Liquid Chromatography-Mass Spectrometry and High Resolution-Mass Spectrometry analysis identified the presence of four N-feruloyltyramine derivatives, namely trans-N-feruloyl-3-hydroxytyramine (1), trans-N-coumaroyltyramine (2), trans-N-feruloyltyramine (3) and trans-N-feruloyl-3-ethoxytyramine (4) in the alkaloid extract. Compounds 2 and 3 have not been yet reported in the alkaloid extract of T. terristris. In silico analysis revealed therapeutic potential of N-feruloyltyramine derivatives and strong binding efficiency to both chains of Tumor Necrosis Factor Receptor 1. Treatment of alkaloids extract to Jurkat E6-1 clone induced dose-dependent cytotoxicity (LC50 140.4 µg mL-1). Jurkat cells treated with alkaloids extract at sub-lethal concentration showed DNA fragmentation, enhancement in caspase-3 activity and phosphatidylserine translocation (apoptosis indicator) compared to control cells. Gene expression analysis using Human Apoptosis RT2 Profiler PCR Array analysis upon alkaloid treatment was found to significantly alter expression of critical genes such as TNFR1, FADD, AIFM, CASP8, TP53, DFFA and NFKB1. These genes are predicted to mediate apoptotic cell death via both intrinsic and extrinsic apoptosis pathway. In summary, we report the identification of new N-feruloyltyramine derivatives from alkaloid extract of T. terristris fruit with probable anti-leukemic and pharmacological potential.

The burden of disease attributable to ambient PM2.5-bound PAHs exposure in Nagpur, India.

Exposure to PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) can elicit several types of cancer and non-cancer effects. Previous studies reported substantial burdens of PAH-induced lung cancer, but the burdens of other cancer types and non-cancer effects remain unknown. Thus, we estimate the cancer and non-cancer burden of disease, in disability-adjusted life years (DALYs), attributable to ambient PM2.5-bound PAHs exposure in Nagpur district, India, using risk-based approach. We measured thirteen PAHs in airborne PM2.5 sampled from nine sites covering urban, peri-urban and rural areas, from February 2013 to June 2014. We converted PAHs concentrations to benzo[a]pyrene equivalence (B[a]Peq) for cancer and non-cancer effects using relative potency factors, and relative toxicity factors derived from quantitative structure-activity relationships, respectively. We calculated time-weighted exposure to B[a]Peq, averaged over 30 years, and adjusted for early-life susceptibility to cancer. We estimated the DALYs/year using B[a]Peq exposure levels, published toxicity data, and severity of the diseases from Global Burden of Disease 2016 database. The annual average concentration of total PM2.5-bound PAHs was 458 ±â€¯246 ng/m3 and resulted in 49,500 DALYs/year (0.011 DALYs/person/year). The PAH-related DALYs followed this order: developmental (mostly cardiovascular) impairments (55.1%) > cancer (26.5%) or lung cancer (23.1%) > immunological impairments (18.0%) > reproductive abnormalities (0.4%).

The gains in life expectancy by ambient PM2.5 pollution reductions in localities in Nigeria.

Global burden of disease estimates reveal that people in Nigeria are living shorter lifespan than the regional or global average life expectancy. Ambient air pollution is a top risk factor responsible for the reduced longevity. But, the magnitude of the loss or the gains in longevity accruing from the pollution reductions, which are capable of driving mitigation interventions in Nigeria, remain unknown. Thus, we estimate the loss, and the gains in longevity resulting from ambient PM2.5 pollution reductions at the local sub-national level using life table approach. Surface average PM2.5 concentration datasets covering Nigeria with spatial resolution of ∼1 km were obtained from the global gridded concentration fields, and combined with ∼1 km gridded population of the world (GPWv4), and global administrative unit layers (GAUL) for territorial boundaries classification. We estimate the loss or gains in longevity using population-weighted average pollution level and baseline mortality data for cardiopulmonary disease and lung cancer in adults ≥25 years and for respiratory infection in children under 5. As at 2015, there are six "highly polluted", thirty "polluted" and one "moderately polluted" States in Nigeria. People residing in these States lose ∼3.8-4.0, 3.0-3.6 and 2.7 years of life expectancy, respectively, due to the pollution exposure. But, assuming interventions achieve global air quality guideline of 10 µg/m3, longevity would increase by 2.6-2.9, 1.9-2.5 and 1.6 years for people in the State-categories, respectively. The longevity gains are indeed high, but to achieve them, mitigation interventions should target emission sources having the highest population exposures.

Role of fluoride induced histone trimethylation in development of skeletal fluorosis.

Chronic exposure to fluoride has been associated with the development of skeletal fluorosis. Limited reports are available on fluoride induced histone modification. However, the role of histone modification in the pathogenesis of skeletal fluorosis is not investigated. In the present study, we have investigated the role of fluoride induced histone modification on fluorosis development using human osteosarcoma (HOS) cell line. The expression of histone methyltransferases (EHMT1 and EHZ2) and level of global histone trimethylation (H3K9 and H3K27) have been assessed and observed to be increased significantly after fluoride exposure (8 mg/L). EpiTect chromatin immunoprecipitation (CHIP) qPCR Array (Human TGFß/BMP signaling pathway) was performed to assess the H3K9 trimethylation at promoter regions of pathway-specific genes. H3K9 ChIP PCR array analysis identified hyper H3K9 trimethylation in promoter regions of TGFBR2 and SMAD3. qPCR and STRING analysis was carried out to determine the repressive epigenetic effect of H3K9 trimethylation on expression pattern and functional association of identified genes. Identified genes (TGFBR2 and SMAD3) showed down-regulation which confirms the repressive epigenetic effect of promoter H3K9 hyper trimethylation. Expression of two other vital genes COL1A1 and MMP13 involved in TGFBR2-SMAD signaling pathway was also found to be down-regulated with a decrease in expression of TGFBR2 and SMAD3. STRING analysis revealed functional association and involvement of identified genes TGFBR2, SMAD3, COL1A1 and MMP13 in the collagen and cartilage development/morphogenesis, connective tissue formation, bio-mineral tissue development, endochondral bone formation, bone and skeletal morphogenesis. In conclusion, present investigation is a first attempt to link fluoride induced hyper H3K9 tri-methylation mediated repression of TGFBR2 and SMAD3 with the development of skeletal fluorosis.

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 Parkinson's 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.

Manganese-Induced Neurotoxicity and Alterations in Gene Expression in Human Neuroblastoma SH-SY5Y Cells.

Manganese (Mn) is an essential trace element required for many physiological functions including proper biochemical and cellular functioning of the central nervous system (CNS). However, exposure to excess level of Mn through occupational settings or from environmental sources has been associated with neurotoxicity. The cellular and molecular mechanism of Mn-induced neurotoxicity remains unclear. In the current study, we investigated the effects of 30-day exposure to a sub-lethal concentration of Mn (100 µM) in human neuroblastoma cells (SH-SY5Y) using transcriptomic approach. Microarray analysis revealed differential expression of 1057 transcripts in Mn-exposed SH-SY5Y cells as compared to control cells. Gene functional annotation cluster analysis exhibited that the differentially expressed genes were associated with several biological pathways. Specifically, genes involved in neuronal pathways including neuron differentiation and development, regulation of neurogenesis, synaptic transmission, and neuronal cell death (apoptosis) were found to be significantly altered. KEGG pathway analysis showed upregulation of p53 signaling pathways and neuroactive ligand-receptor interaction pathways, and downregulation of neurotrophin signaling pathway. On the basis of the gene expression profile, possible molecular mechanisms underlying Mn-induced neuronal toxicity were predicted.