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  1. Article ; Online: NADPH Oxidase-Mediated Superoxide Production by Intermediary Bacterial Metabolites of Dibenzofuran: A Potential Cause for Trans-Mitochondrial Membrane Potential (ΔΨm) Collapse in Human Hepatoma Cells.

    Jaiswal, Prashant Kumar / Gupta, Jyotsana / Shahni, Shweta / Thakur, Indu Shekhar

    Toxicological sciences : an official journal of the Society of Toxicology

    2022  Volume 148, Issue 1, Page(s) 330

    Language English
    Publishing date 2022-11-03
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfv217
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    Zs.A 1709: Show issues Location:
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  2. Article ; Online: A Non-Instrumental Green Analytical Method Based on Surfactant-Assisted Dispersive Liquid-Liquid Microextraction-Thin-Layer Chromatography-Smartphone-Based Digital Image Colorimetry(SA-DLLME-TLC-SDIC) for Determining Favipiravir in Biological Samples.

    Jain, Bharti / Jain, Rajeev / Jaiswal, Prashant Kumar / Zughaibi, Torki / Sharma, Tanvi / Kabir, Abuzar / Singh, Ritu / Sharma, Shweta

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 2

    Abstract: Favipiravir (FAV) has become a promising antiviral agent for the treatment of COVID-19. Herein, a green, fast, high-sample-throughput, non-instrumental, and affordable analytical method is proposed based on surfactant-assisted dispersive liquid-liquid ... ...

    Abstract Favipiravir (FAV) has become a promising antiviral agent for the treatment of COVID-19. Herein, a green, fast, high-sample-throughput, non-instrumental, and affordable analytical method is proposed based on surfactant-assisted dispersive liquid-liquid microextraction (SA-DLLME) combined with thin-layer chromatography-digital image colourimetry (TLC-DIC) for determining favipiravir in biological and pharmaceutical samples. Triton X-100 and dichloromethane (DCM) were used as the disperser and extraction solvents, respectively. The extract obtained after DLLME procedure was spotted on a TLC plate and allowed to develop with a mobile phase of chloroform:methanol (8:2,
    MeSH term(s) Humans ; Surface-Active Agents ; Colorimetry ; Chromatography, Thin Layer ; Liquid Phase Microextraction/methods ; Smartphone ; Pandemics ; COVID-19 ; Solvents ; Chromatography, High Pressure Liquid ; Pulmonary Surfactants ; Lipoproteins ; Pharmaceutical Preparations ; Limit of Detection
    Chemical Substances Surface-Active Agents ; favipiravir (EW5GL2X7E0) ; Solvents ; Pulmonary Surfactants ; Lipoproteins ; Pharmaceutical Preparations
    Language English
    Publishing date 2023-01-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28020529
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    Zs.MO 81: Show issues

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  3. Article ; Online: Biochemical characteristics of the chondrocyte-enriched SNORC protein and its transcriptional regulation by SOX9.

    Jaiswal, Prashant Kumar / Aljebali, Latifa / Gaumond, Marie-Hélène / Oh, Chun-do / Yasuda, Hideyo / Moffatt, Pierre

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 7790

    Abstract: Snorc (Small NOvel Rich in Cartilage) has been identified as a chondrocyte-specific gene in the mouse. Yet little is known about the SNORC protein biochemical properties, and mechanistically how the gene is regulated transcriptionally in a tissue- ... ...

    Abstract Snorc (Small NOvel Rich in Cartilage) has been identified as a chondrocyte-specific gene in the mouse. Yet little is known about the SNORC protein biochemical properties, and mechanistically how the gene is regulated transcriptionally in a tissue-specific manner. The goals of the present study were to shed light on those important aspects. The chondrocyte nature of Snorc expression was confirmed in mouse and rat tissues, in differentiated (day 7) ATDC5, and in RCS cells where it was constitutive. Topological mapping and biochemical analysis brought experimental evidences that SNORC is a type I protein carrying a chondroitin sulfate (CS) attached to serine 44. The anomalous migration of SNORC on SDS-PAGE was due to its primary polypeptide features, suggesting no additional post-translational modifications apart from the CS glycosaminoglycan. A highly conserved SOX9-binding enhancer located in intron 1 was necessary to drive transcription of Snorc in the mouse, rat, and human. The enhancer was active independently of orientation and whether located in a heterologous promoter or intron. Crispr-mediated inactivation of the enhancer in RCS cells caused reduction of Snorc. Transgenic mice carrying the intronic multimerized enhancer drove high expression of a βGeo reporter in chondrocytes, but not in the hypertrophic zone. Altogether these data confirmed the chondrocyte-specific nature of Snorc and revealed dependency on the intronic enhancer binding of SOX9 for transcription.
    MeSH term(s) Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cells, Cultured ; Chondrocytes/metabolism ; Chondroitin Sulfates/metabolism ; Gene Expression Regulation ; Humans ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Transgenic ; Open Reading Frames ; Protein Binding ; Protein Domains ; Proteoglycans/chemistry ; Proteoglycans/genetics ; Proteoglycans/metabolism ; Rats ; SOX9 Transcription Factor/metabolism ; Transcription Initiation Site ; Transcription, Genetic
    Chemical Substances Membrane Proteins ; Proteoglycans ; SOX9 Transcription Factor ; Snorc protein, mouse ; Sox9 protein, mouse ; Chondroitin Sulfates (9007-28-7)
    Language English
    Publishing date 2020-05-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-64640-x
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  4. Article ; Online: NADPH Oxidase-Mediated Superoxide Production by Intermediary Bacterial Metabolites of Dibenzofuran: A Potential Cause for Trans-Mitochondrial Membrane Potential (ΔΨm) Collapse in Human Hepatoma Cells.

    Jaiswal, Prashant Kumar / Gupta, Jyotsana / Shahni, Shweta / Thakur, Indu Shekhar

    Toxicological sciences : an official journal of the Society of Toxicology

    2015  Volume 147, Issue 1, Page(s) 17–27

    Abstract: Dibenzofuran is a direct precursor of extremely toxic compounds such as dioxins. It is widely distributed persistent organic pollutant in environment that potentiate oxidative stress, apoptosis, and necrosis through bioactivation in HepG2 cells. An ... ...

    Abstract Dibenzofuran is a direct precursor of extremely toxic compounds such as dioxins. It is widely distributed persistent organic pollutant in environment that potentiate oxidative stress, apoptosis, and necrosis through bioactivation in HepG2 cells. An alkalotolerent Pseudomonas strain ISTDF1 can metabolize dibenzofuran as a sole source of carbon and energy through diverse dioxygenation. However, there is a paucity of information about the potential toxic effects of the intermediary metabolites that are formed during treatment with dibenzofuran. We have assessed and discovered the potential mechanism of toxicity induced by metabolites of dibenzofuran that were formed at 18 and 36 h. Cell viability, CYP1A2 induction, ROS activity, Superoxide production, mitochondrial NADPH oxidase activity, and mitochondrial trans-membrane potential were studied using different assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), confocal laser scanning microscopy, and flow cytometry. Analysis revealed formation of 2-(1-carbonyl methylidine)-2,3-dihydrobenzofuranlidene after 18 h of bacterial treatment due to oxygenation at carbon (C3-C4). This compound induces higher mitochondrial NADPH oxidase-dependent superoxide production that makes it more toxic than the parent compound. It was evident that after 36 h of bacterial treatment, toxicity induced by dibenzofuran and its metabolites was completely removed. This study highlights the fact that despite of efficient biodegradation of toxicants, bioactive toxic intermediates can be formed. Therefore, it is necessary to assess the toxicity of each intermediary for complete mitigation of associated risk.
    MeSH term(s) Benzofurans/metabolism ; Benzofurans/toxicity ; Biodegradation, Environmental ; Carcinoma, Hepatocellular/enzymology ; Carcinoma, Hepatocellular/metabolism ; Cell Line, Tumor ; Cell Survival ; Cytochrome P-450 CYP1A2/biosynthesis ; Hep G2 Cells ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria, Liver/enzymology ; Mitochondria, Liver/metabolism ; NADPH Oxidases/metabolism ; Pseudomonas/metabolism ; Reactive Oxygen Species/metabolism ; Superoxides/metabolism
    Chemical Substances Benzofurans ; Reactive Oxygen Species ; Superoxides (11062-77-4) ; dibenzofuran (8U54U639VI) ; CYP1A2 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; NADPH Oxidases (EC 1.6.3.-)
    Language English
    Publishing date 2015-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfv107
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    Zs.A 1709: Show issues Location:
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  5. Article: Isolation and characterization of dibenzofuran-degrading Serratia marcescens from alkalophilic bacterial consortium of the chemostat.

    Jaiswal, Prashant Kumar / Thakur, Indu Shekhar

    Current microbiology

    2007  Volume 55, Issue 5, Page(s) 447–454

    Abstract: Alkalophilic bacterial consortium developed by continuous enrichment in the chemostat in presence of 4-chlorosalicylic acid as sole source of carbon and energy contained six bacterial strains, Micrococcus luteus (csa101), Deinococcus radiothilus (csa102), ...

    Abstract Alkalophilic bacterial consortium developed by continuous enrichment in the chemostat in presence of 4-chlorosalicylic acid as sole source of carbon and energy contained six bacterial strains, Micrococcus luteus (csa101), Deinococcus radiothilus (csa102), csa103 (Burkholderia gladioli), Alloiococcus otilis (csa104), Micrococcus diversus (csa105), Micrococcus luteus (csa106), identified by the Biolog test method. The strains were tested for utilization of organic compounds in which one of the strains (csa101) had higher potency to utilize dibenzofuran (DF) as sole carbon and energy source identified as Serratia marcescens on the basis of 16S rDNA. The degradation of DF by bacterial strain proceeded through an oxidative route as indicated by 2,2'3-trihydroxybiphenyl, 2-hydroxy-6-(2-hydroxyphenyl)-6-oxo-2,4-hexadienoic acid, salicylic acid, and catechol, which was identified by gas chromatography-mass spectrometry.
    MeSH term(s) Bacterial Proteins/isolation & purification ; Bacterial Proteins/metabolism ; Benzofurans/chemistry ; Benzofurans/metabolism ; Biodegradation, Environmental ; Electrophoresis, Polyacrylamide Gel ; Enzymes/isolation & purification ; Enzymes/metabolism ; Gas Chromatography-Mass Spectrometry ; Molecular Structure ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Serratia marcescens/genetics ; Serratia marcescens/isolation & purification ; Serratia marcescens/metabolism
    Chemical Substances Bacterial Proteins ; Benzofurans ; Enzymes ; RNA, Ribosomal, 16S ; dibenzofuran (8U54U639VI)
    Language English
    Publishing date 2007-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 134238-1
    ISSN 1432-0991 ; 0343-8651
    ISSN (online) 1432-0991
    ISSN 0343-8651
    DOI 10.1007/s00284-007-9013-8
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    Zs.A 1446: Show issues Location:
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  6. Article ; Online: Hypoxia modulates cell migration and proliferation in placenta-derived mesenchymal stem cells.

    Li, Li / Jaiswal, Prashant Kumar / Makhoul, Georges / Jurakhan, Rishi / Selvasandran, Kaviyanka / Ridwan, Khalid / Cecere, Renzo

    The Journal of thoracic and cardiovascular surgery

    2017  Volume 154, Issue 2, Page(s) 543–552.e3

    Abstract: Objectives: For more than a decade, stem cells isolated from different tissues have been evaluated in cell therapy. Among them, the human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were investigated extensively in the treatment of myocardial ... ...

    Abstract Objectives: For more than a decade, stem cells isolated from different tissues have been evaluated in cell therapy. Among them, the human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were investigated extensively in the treatment of myocardial infarction. Recently, the human placenta-derived mesenchymal stem cells (hPD-MSCs), which are readily available from a biological waste, appear to be a viable alternative to hBM-MSCs.
    Methods: C-X-C chemokine receptor type 4 (CXCR4) gene expression and localization were detected and validated in hPD-MSCs and hBM-MSCs via polymerase chain reaction and immunofluorescence. Subsequently, cell culture conditions for CXCR4 expression were optimized in stromal-derived factor-1 alpha (SDF1-α), glucose, and cobalt chloride (CoCl
    Results: CXCR4 was expressed on both hPD-MSCs and hBM-MSCs at the basal level. HPD-MSCs were shown to have a greater sensitivity to SDF-1α-dependent cell migration compared with hBM-MSCs. In addition, CXCR4 expression was significantly greater in both hPD-MSCs and hBM-MSCs with SDF-1α or CoCl
    Conclusions: Our current results suggest that hPD-MSCs could represent a viable and effective alternative to hBM-MSCs for translational studies in cardiocellular repair.
    MeSH term(s) Blotting, Western ; Bone Marrow Cells ; Cell Movement ; Cell Proliferation ; Cell Survival ; Female ; Humans ; Hypoxia/physiopathology ; Mesenchymal Stem Cells/physiology ; Placenta/cytology ; Pregnancy ; Receptors, CXCR4/metabolism ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances CXCR4 protein, human ; Receptors, CXCR4
    Language English
    Publishing date 2017-04-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3104-5
    ISSN 1097-685X ; 0022-5223
    ISSN (online) 1097-685X
    ISSN 0022-5223
    DOI 10.1016/j.jtcvs.2017.03.141
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  7. Article ; Online: Dibenzofuran induces oxidative stress, disruption of trans-mitochondrial membrane potential (ΔΨm) and G1 arrest in human hepatoma cell line.

    Jaiswal, Prashant Kumar / Srivastava, Shaili / Gupta, Jyotsana / Thakur, Indu Shekhar

    Toxicology letters

    2012  Volume 214, Issue 2, Page(s) 137–144

    Abstract: Dioxins are a class of extremely toxic environmentally persistent pollutant, comprised of halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls. Despite significant human exposure via multiple routes, very little is known about toxicity induced by ... ...

    Abstract Dioxins are a class of extremely toxic environmentally persistent pollutant, comprised of halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls. Despite significant human exposure via multiple routes, very little is known about toxicity induced by dibenzofuran (DF). Current study shed lights on the potential toxicity mechanism of DF using human hepatoma cell line (HepG2). It was observed that the exposure to DF potentiate oxidative stress, apoptosis and necrosis at 10μM within 8h in HepG2 cells. Interestingly, when we pre-incubated the cells with α-NF (1nM) for 12h, an aromatic hydrocarbon receptor antagonist, the IC(50) of DF increased by 14 folds indicating the cytoprotective ability of α-NF from DF induced toxicity. Furthermore, three additional metabolites were observed while studying the metabolic profile of DF in HepG2 cells with and without pre-incubation with α-NF using chromatography-mass spectroscopy (GC-MS). Of these, two metabolites were characterized as dihydroxylated derivative of DF and third metabolite was characterized as quinone derivative of DF. By flow cytometry and confocal laser microscopy analysis we followed the ROS formation after DF (10μM) exposure for 3h. Significantly low ROS was generated in cells which were pre-incubated with α-NF than cells which were not pre-incubated with α-NF underlining the importance of metabolism in DF toxicity. The same pattern of protection was consistent while measuring mitochondrial membrane potential (MMP), i.e., less MMP dip was observed in 'with α-NF pre-incubated and DF (10μM) exposed cells' than 'without α-NF pre-incubated but DF exposed cells'. In cell cycle studies, it was confirmed that cell population of HepG2 at G1 stage progressively increased in number (∼74%) within 24h. Thus, DF and its metabolites induce significantly higher cytotoxicity after metabolism in HepG2 cells than its parent compound (DF) by ROS formation, MMP dip and impaired cell cycle.
    MeSH term(s) Apoptosis/drug effects ; Apoptosis/physiology ; Benzoflavones/pharmacology ; Benzofurans/toxicity ; Cell Cycle Checkpoints/drug effects ; Cell Cycle Checkpoints/physiology ; Cell Survival/drug effects ; Flow Cytometry ; Hep G2 Cells ; Humans ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Logistic Models ; Membrane Potential, Mitochondrial/drug effects ; Membrane Potential, Mitochondrial/physiology ; Microscopy, Confocal ; Mitochondria, Liver/drug effects ; Mitochondria, Liver/metabolism ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Reactive Oxygen Species/metabolism
    Chemical Substances Benzoflavones ; Benzofurans ; Reactive Oxygen Species ; alpha-naphthoflavone (604-59-1) ; dibenzofuran (8U54U639VI)
    Language English
    Publishing date 2012-10-17
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 433788-8
    ISSN 1879-3169 ; 0378-4274
    ISSN (online) 1879-3169
    ISSN 0378-4274
    DOI 10.1016/j.toxlet.2012.08.014
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    Zs.A 1367: Show issues Location:
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  8. Article ; Online: Conditioned medium of H9c2 triggers VEGF dependent angiogenesis by activation of p38/pSTAT3 pathways in placenta derived stem cells for cardiac repair.

    Makhoul, Georges / Jurakhan, Rishi / Jaiswal, Prashant Kumar / Ridwan, Khalid / Li, Li / Selvasandran, Kaviyanka / Duong, Minh / Schwertani, Adel / Cecere, Renzo

    Life sciences

    2016  Volume 153, Page(s) 213–221

    Abstract: Aims: Cardiomyocytes are understood to possess a limited regenerative capacity. Any myocardial insult leads to an irreversible injury. Mesenchymal stem cell differentiation into cardiomyocyte-like cells stands as one of the leading experimental ... ...

    Abstract Aims: Cardiomyocytes are understood to possess a limited regenerative capacity. Any myocardial insult leads to an irreversible injury. Mesenchymal stem cell differentiation into cardiomyocyte-like cells stands as one of the leading experimental therapies. However, a candidate cell source has yet to be defined. Here, we examined the in vitro and in vivo cardiac differentiation potential of human placenta derived stem cells (hPDSCs); a unique, abundant, and non-immunogenic cell source.
    Main methods: H9c2 cell culture medium was applied to hPDSCs at different ratios for a period of 4weeks. In parallel, hPDSCs, human bone marrow stem cells, or cell free culture medium was injected in peri-infarcted regions induced in rat hearts.
    Key findings: In vitro, hPDSCs pre-conditioned with H9c2 cell culture medium proportionally over-expressed alpha sarcoplasmic actinin and displaced connexin 43 from the cytoplasm to the cell membrane. Additionally, pre-conditioning promoted hPDSCs survival and triggered vascular endothelial growth factor (VEGF) dependent angiogenesis by activating the pAkt and p38MAPK/pSTAT3 pathways. In vivo, echocardiography analysis showed a significant improvement in cardiac parameters in the rats injected with hPDSCs, similar to the human bone marrow stem cells injected group. Moreover, hPDSCs detected within rat cardiac tissues expressed troponin I and myosin heavy chain. In accordance with the pre-conditioning findings, VEGF positive neovessels were observed in hearts injected with hPDSCs.
    Significance: hPDSCs have the potential to differentiate into cardiac-like cells and induce angiogenesis via paracrine effects. With the advantages of easy availability and young age, these cells could be more suitable for clinical translation.
    MeSH term(s) Animals ; Culture Media, Conditioned ; Female ; Humans ; Myocardium/cytology ; Neovascularization, Pathologic ; Placenta/cytology ; Pregnancy ; Rats ; Rats, Inbred Lew ; STAT3 Transcription Factor/metabolism ; Stem Cells/cytology ; Vascular Endothelial Growth Factor A/physiology ; p38 Mitogen-Activated Protein Kinases/metabolism
    Chemical Substances Culture Media, Conditioned ; STAT3 Transcription Factor ; STAT3 protein, human ; Vascular Endothelial Growth Factor A ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2016-05-15
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2016.04.009
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  9. Article ; Online: Assessment of Cryptococcus albidus for biopulping of eucalyptus.

    Singhal, Anjali / Jaiswal, Prashant Kumar / Jha, Pawan Kumar / Thapliyal, Alka / Thakur, Indu Shekhar

    Preparative biochemistry & biotechnology

    2013  Volume 43, Issue 8, Page(s) 735–749

    Abstract: Cryptococcus albidus shows delignification activity in nature. It was used for the biopulping of eucalyptus wood (Eucalyptus grandis) to access its potential for industrial application in the pulp and paper industry. Enzyme analysis on days 15, 30, and ... ...

    Abstract Cryptococcus albidus shows delignification activity in nature. It was used for the biopulping of eucalyptus wood (Eucalyptus grandis) to access its potential for industrial application in the pulp and paper industry. Enzyme analysis on days 15, 30, and 60 showed the presence of laccase and xylanase as key enzymes. The production of endo-glucanase (CMCase) and exo-glucanase (FPase) was very low. Scanning electron microscopy (SEM) showed the surface colonization of wood and loosening of wood fibers in C. albidus-treated samples. Fourier-transformation infrared spectroscopy (FT-IR) indicated the chemical modification of eucalyptus wood. Denaturing gradient gel electrophoresis (DGGE) analysis on days 15, 30, and 60 confirmed the presence of C. albidus throughout the experiments. Cryptococcu albidus was able to suppress the growth of a native population. Further, after 60 days both the control and treated eucalyptus wood chips were given kraft pulping treatment. The kappa number of pulp of control wood was 21 and for treated wood was 17. Kappa number is considered a measure of lignin content in wood; hence the treatment of eucalyptus by C. albidus (biopulping) was effective in reducing its lignin content and can be used for biopulping in the pulp and paper industry.
    MeSH term(s) Cryptococcus/chemistry ; Cryptococcus/enzymology ; Endo-1,4-beta Xylanases/chemistry ; Eucalyptus/chemistry ; Fungal Proteins/chemistry ; Hydrolysis ; Laccase/chemistry ; Lignin/metabolism ; Microscopy, Electron, Scanning ; Paper ; Spectroscopy, Fourier Transform Infrared ; Wood/metabolism
    Chemical Substances Fungal Proteins ; Lignin (9005-53-2) ; Laccase (EC 1.10.3.2) ; Endo-1,4-beta Xylanases (EC 3.2.1.8)
    Language English
    Publishing date 2013
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1322522-4
    ISSN 1532-2297 ; 1082-6068
    ISSN (online) 1532-2297
    ISSN 1082-6068
    DOI 10.1080/10826068.2013.771784
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  10. Article: Dibenzofuran induces oxidative stress, disruption of trans-mitochondrial membrane potential (ΔΨm) and G1 arrest in human hepatoma cell line

    Jaiswal, Prashant Kumar / Srivastava, Shaili / Gupta, Jyotsana / Thakur, Indu Shekhar

    Toxicology letters. 2012 Oct. 17, v. 214, no. 2

    2012  

    Abstract: Dioxins are a class of extremely toxic environmentally persistent pollutant, comprised of halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls. Despite significant human exposure via multiple routes, very little is known about toxicity induced by ... ...

    Abstract Dioxins are a class of extremely toxic environmentally persistent pollutant, comprised of halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls. Despite significant human exposure via multiple routes, very little is known about toxicity induced by dibenzofuran (DF). Current study shed lights on the potential toxicity mechanism of DF using human hepatoma cell line (HepG2). It was observed that the exposure to DF potentiate oxidative stress, apoptosis and necrosis at 10μM within 8h in HepG2 cells. Interestingly, when we pre-incubated the cells with α-NF (1nM) for 12h, an aromatic hydrocarbon receptor antagonist, the IC₅₀ of DF increased by 14 folds indicating the cytoprotective ability of α-NF from DF induced toxicity. Furthermore, three additional metabolites were observed while studying the metabolic profile of DF in HepG2 cells with and without pre-incubation with α-NF using chromatography–mass spectroscopy (GC–MS). Of these, two metabolites were characterized as dihydroxylated derivative of DF and third metabolite was characterized as quinone derivative of DF. By flow cytometry and confocal laser microscopy analysis we followed the ROS formation after DF (10μM) exposure for 3h. Significantly low ROS was generated in cells which were pre-incubated with α-NF than cells which were not pre-incubated with α-NF underlining the importance of metabolism in DF toxicity. The same pattern of protection was consistent while measuring mitochondrial membrane potential (MMP), i.e., less MMP dip was observed in ‘with α-NF pre-incubated and DF (10μM) exposed cells’ than ‘without α-NF pre-incubated but DF exposed cells’. In cell cycle studies, it was confirmed that cell population of HepG2 at G1 stage progressively increased in number (∼74%) within 24h. Thus, DF and its metabolites induce significantly higher cytotoxicity after metabolism in HepG2 cells than its parent compound (DF) by ROS formation, MMP dip and impaired cell cycle.
    Keywords antagonists ; apoptosis ; cell cycle ; confocal laser scanning microscopy ; cytotoxicity ; dibenzofuran ; dioxins ; flow cytometry ; gas chromatography-mass spectrometry ; hepatoma ; human cell lines ; humans ; inhibitory concentration 50 ; membrane potential ; metabolism ; metabolites ; mitochondrial membrane ; necrosis ; oxidative stress ; pollutants ; tumor necrosis factors
    Language English
    Dates of publication 2012-1017
    Size p. 137-144.
    Publishing place Elsevier Ireland Ltd
    Document type Article
    ZDB-ID 433788-8
    ISSN 1879-3169 ; 0378-4274
    ISSN (online) 1879-3169
    ISSN 0378-4274
    DOI 10.1016/j.toxlet.2012.08.014
    Database NAL-Catalogue (AGRICOLA)

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