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  1. Article ; Online: The Anti-Proliferative Lichen-Compound Protolichesterinic Acid Inhibits Oxidative Phosphorylation and Is Processed via the Mercapturic Pathway in Cancer Cells.

    Jóhannsson, Freyr / Cherek, Paulina / Xu, Maonian / Rolfsson, Óttar / Ögmundsdóttir, Helga M

    Planta medica

    2021  Volume 88, Issue 11, Page(s) 891–898

    Abstract: The lichen compound protolichesterinic acid (PA) has an anti-proliferative effect against several cancer cell lines of different origin. This effect cannot be explained by the known inhibitory activity of PA against 5- and 12-lipoxygenases. The aim was ... ...

    Abstract The lichen compound protolichesterinic acid (PA) has an anti-proliferative effect against several cancer cell lines of different origin. This effect cannot be explained by the known inhibitory activity of PA against 5- and 12-lipoxygenases. The aim was therefore to search for mechanisms for the anti-proliferative activity of PA. Two cancer cell lines of different origin, both sensitive to anti-proliferative effects of PA, were selected for this study, T-47D from breast cancer and AsPC-1 from pancreatic cancer. Morphological changes were assessed by transmission electron microscopy, HPLC coupled with TOF spectrometry was used for metabolomics, mitochondrial function was measured using the Agilent Seahorse XFp Real-time ATP assay and glucose/lactate levels by radiometry. Levels of glutathione, NADP/NADPH and reactive oxygen species [ROS] were measured by luminescence. Following exposure to PA both cell lines showed structural changes in mitochondria that were in line with a measured reduction in oxidative phosphorylation and increased glycolysis. These changes were more marked in T-47D, which had poorer mitochondrial function at baseline. PA was processed and expelled from the cells via the mercapturic pathway, which consumes glutathione. Nevertheless, glutathione levels were increased after 24 hours of exposure to PA, implying enhanced synthesis. Redox balance was not much affected and ROS levels were not increased. We conclude that PA is metabolically processed and expelled from cells, leading indirectly to increased glutathione levels with minimal effects on redox balance. The most marked effect was on mitochondrial structure and metabolic function implying that effects of PA may depend on mitochondrial fitness.
    MeSH term(s) 4-Butyrolactone/analogs & derivatives ; Cell Proliferation ; Glutathione/metabolism ; Lichens/chemistry ; Neoplasms ; Oxidation-Reduction ; Oxidative Phosphorylation ; Reactive Oxygen Species/metabolism
    Chemical Substances Reactive Oxygen Species ; protolichesterinic acid (1448-96-0) ; Glutathione (GAN16C9B8O) ; 4-Butyrolactone (OL659KIY4X)
    Language English
    Publishing date 2021-09-14
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 123545-x
    ISSN 1439-0221 ; 0032-0943
    ISSN (online) 1439-0221
    ISSN 0032-0943
    DOI 10.1055/a-1579-6454
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Short Depuration of Oysters Intended for Human Consumption Is Effective at Reducing Exposure to Nanoplastics.

    Ribeiro, Francisca / Mitrano, Denise M / Hacker, Christian / Cherek, Paulina / Brigden, Kevin / Kaserzon, Sarit Leat / Thomas, Kevin V / Galloway, Tamara S

    Environmental science & technology

    2022  Volume 56, Issue 23, Page(s) 16716–16725

    Abstract: Nanoplastics (NPs; <1 μm) have greater availability to marine organisms than microplastics (1-5000 μm). Understanding NP uptake and depuration in marine organisms intended for human consumption is imperative for food safety, but until now it has been ... ...

    Abstract Nanoplastics (NPs; <1 μm) have greater availability to marine organisms than microplastics (1-5000 μm). Understanding NP uptake and depuration in marine organisms intended for human consumption is imperative for food safety, but until now it has been limited due to analytical constraints. Oysters (
    Language English
    Publishing date 2022-11-16
    Publishing country United States
    Document type Journal Article
    ISSN 1520-5851
    ISSN (online) 1520-5851
    DOI 10.1021/acs.est.2c02269
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cytotoxic effects of halogenated tin phosphinoyldithioformate complexes against several cancer cell lines.

    Balogová, Michaela / Sharma, Shubham / Cherek, Paulina / Ólafsson, Sigurjón N / Jónsdóttir, Sigrídur / Ögmundsdóttir, Helga M / Damodaran, Krishna K

    Dalton transactions (Cambridge, England : 2003)

    2022  Volume 51, Issue 34, Page(s) 13119–13128

    Abstract: Organotin complexes are studied as promising alternatives to the anticancer drug cisplatin. We report two monoorganotin(IV) complexes based on a dibenzyl phosphinoyldithioformate (H-DBPTF) ligand, containing either bromide (Sn-DBPTF-1) or chloride (Sn- ... ...

    Abstract Organotin complexes are studied as promising alternatives to the anticancer drug cisplatin. We report two monoorganotin(IV) complexes based on a dibenzyl phosphinoyldithioformate (H-DBPTF) ligand, containing either bromide (Sn-DBPTF-1) or chloride (Sn-DBPTF-2) anions. The complexes were characterized by standard analytical techniques and the structural details of these complexes were elucidated by single crystal X-ray diffraction. Sn-DBPTF-1 was cytotoxic at IC
    MeSH term(s) Female ; Humans ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Ovarian Neoplasms ; Tin/pharmacology
    Chemical Substances Antineoplastic Agents ; Tin (7440-31-5)
    Language English
    Publishing date 2022-08-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472887-4
    ISSN 1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
    ISSN (online) 1477-9234 ; 1364-5447
    ISSN 0300-9246 ; 1477-9226
    DOI 10.1039/d2dt01127a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The Anti-Proliferative Lichen-Compound Protolichesterinic Acid Inhibits Oxidative Phosphorylation and Is Processed via the Mercapturic Pathway in Cancer Cells

    Jóhannsson, Freyr / Cherek, Paulina / Xu, Maonian / Rolfsson, Óttar / Ögmundsdóttir, Helga M.

    Planta Medica

    2021  Volume 88, Issue 11, Page(s) 891–898

    Abstract: The lichen compound protolichesterinic acid (PA) has an anti-proliferative effect against several cancer cell lines of different origin. This effect cannot be explained by the known inhibitory activity of PA against 5- and 12-lipoxygenases. The aim was ... ...

    Abstract The lichen compound protolichesterinic acid (PA) has an anti-proliferative effect against several cancer cell lines of different origin. This effect cannot be explained by the known inhibitory activity of PA against 5- and 12-lipoxygenases. The aim was therefore to search for mechanisms for the anti-proliferative activity of PA. Two cancer cell lines of different origin, both sensitive to anti-proliferative effects of PA, were selected for this study, T-47D from breast cancer and AsPC-1 from pancreatic cancer. Morphological changes were assessed by transmission electron microscopy, HPLC coupled with TOF spectrometry was used for metabolomics, mitochondrial function was measured using the Agilent Seahorse XFp Real-time ATP assay and glucose/lactate levels by radiometry. Levels of glutathione, NADP/NADPH and reactive oxygen species [ROS] were measured by luminescence. Following exposure to PA both cell lines showed structural changes in mitochondria that were in line with

    a measured reduction in oxidative phosphorylation and increased glycolysis. These changes were more marked in T-47D, which had poorer mitochondrial function at baseline. PA was processed and expelled from the cells via the mercapturic pathway, which consumes glutathione. Nevertheless, glutathione levels were increased after 24 hours of exposure to PA, implying enhanced synthesis. Redox balance was not much affected and ROS levels were not increased. We conclude that PA is metabolically processed and expelled from cells, leading indirectly to increased glutathione levels with minimal effects on redox balance. The most marked effect was on mitochondrial structure and metabolic function implying that effects of PA may depend on mitochondrial fitness.
    Keywords Protolichesterinic acid ; mitochondria ; cancer ; metabolism ; Parmeliaceae
    Language English
    Publishing date 2021-09-14
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 123545-x
    ISSN 1439-0221 ; 0032-0943
    ISSN (online) 1439-0221
    ISSN 0032-0943
    DOI 10.1055/a-1579-6454
    Database Thieme publisher's database

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  5. Article ; Online: Combined artificial high-silicate medium and LED illumination promote carotenoid accumulation in the marine diatom Phaeodactylum tricornutum.

    Yi, Zhiqian / Su, Yixi / Cherek, Paulina / Nelson, David R / Lin, Jianping / Rolfsson, Ottar / Wu, Hua / Salehi-Ashtiani, Kourosh / Brynjolfsson, Sigurdur / Fu, Weiqi

    Microbial cell factories

    2019  Volume 18, Issue 1, Page(s) 209

    Abstract: Background: Diatoms, which can accumulate large amounts of carotenoids, are a major group of microalgae and the dominant primary producer in marine environments. Phaeodactylum tricornutum, a model diatom species, acquires little silicon for its growth ... ...

    Abstract Background: Diatoms, which can accumulate large amounts of carotenoids, are a major group of microalgae and the dominant primary producer in marine environments. Phaeodactylum tricornutum, a model diatom species, acquires little silicon for its growth although silicon is known to contribute to gene regulation and play an important role in diatom intracellular metabolism. In this study, we explored the effects of artificial high-silicate medium (i.e. 3.0 mM sodium metasilicate) and LED illumination conditions on the growth rate and pigment accumulation in P. tricornutum, which is the only known species so far that can grow without silicate. It's well known that light-emitting diodes (LEDs) as novel illuminants are emerging to be superior monochromatic light sources for algal cultivation with defined and efficient red and blue lights.
    Results: Firstly, we cultivated P. tricornutum in a synthetic medium supplemented with either 0.3 mM or 3.0 mM silicate. The morphology and size of diatom cells were examined: the proportion of the oval and triradiate cells decreased while the fusiform cells increased with more silicate addition in high-silicate medium; the average length of fusiform cells also slightly changed from 14.33 µm in 0.3 mM silicate medium to 12.20 µm in 3.0 mM silicate medium. Then we cultivated P. tricornutum under various intensities of red light in combination with the two different levels of silicate in the medium. Higher biomass productivity also achieved in 3.0 mM silicate medium than in 0.3 mM silicate medium under red LED light irradiation at 128 μmol/m
    Conclusion: High-silicate medium and blue light increased biomass and fucoxanthin production in P. tricornutum under high light conditions and this strategy may be beneficial for large-scale production of fucoxanthin in diatoms.
    MeSH term(s) Carotenoids/chemistry ; Carotenoids/metabolism ; Diatoms/chemistry ; Diatoms/metabolism ; Light ; Silicates/chemistry ; Silicates/metabolism
    Chemical Substances Silicates ; Carotenoids (36-88-4)
    Language English
    Publishing date 2019-12-02
    Publishing country England
    Document type Journal Article
    ISSN 1475-2859
    ISSN (online) 1475-2859
    DOI 10.1186/s12934-019-1263-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Innovative in vitro method to study ventilator induced lung injury.

    Joelsson, Jon P / Myszor, Iwona T / Arason, Ari J / Ingthorsson, Saevar / Cherek, Paulina / Windels, Gabriel S / Leosson, Kristjan / Gudmundsson, Gudmundur H / Gudjonsson, Thorarinn / Karason, Sigurbergur

    ALTEX

    2019  Volume 36, Issue 4, Page(s) 634–642

    Abstract: Mechanical ventilation (MV) is a life-saving therapy for critically ill patients, alleviating the work of breathing and supporting adequate gas exchange. However, MV can cause ventilator induced lung injury (VILI) by baro/volu- and atelectrauma, even ... ...

    Abstract Mechanical ventilation (MV) is a life-saving therapy for critically ill patients, alleviating the work of breathing and supporting adequate gas exchange. However, MV can cause ventilator induced lung injury (VILI) by baro/volu- and atelectrauma, even lead to acute respiratory distress syndrome (ARDS), and substantially augment mortality. There is a need for specific biomarkers and novel research platforms for VILI/ARDS research to study these detrimental disorders and seek ways to avoid or prevent them. Previous in vitro studies on bronchial epithelium, cultured in air-liquid interface (ALI) conditions, have generally utilized static or constant pressure.  We have developed a Cyclical Pressure ALI Device (CPAD) that enables cyclical stress on ALI cultured human bronchial cells, with the aim of mimicking the effects of MV. Using CPAD we were able to analyze differentially expressed VILI/ARDS and innate immunity associated genes along with increased expression of associated proteins. CPAD provides an easy and accessible way to analyze functional and phenotypic changes that occur during VILI and may provide a platform for future drug testing.
    MeSH term(s) Acute Lung Injury/etiology ; Acute Lung Injury/mortality ; Biomarkers ; Bronchi/cytology ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells/cytology ; Humans ; Immunoblotting ; Maximal Respiratory Pressures ; Microscopy, Confocal ; Microscopy, Electron, Transmission ; Phenotype ; Positive-Pressure Respiration, Intrinsic ; Printing, Three-Dimensional ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Tidal Volume ; Ventilator-Induced Lung Injury/complications ; Ventilator-Induced Lung Injury/mortality
    Chemical Substances Biomarkers
    Language English
    Publishing date 2019-06-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 165707-0
    ISSN 1868-596X ; 1018-4562 ; 0946-7785
    ISSN 1868-596X ; 1018-4562 ; 0946-7785
    DOI 10.14573/altex.1901182
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia.

    Arason, Ari Jon / Joelsson, Jon Petur / Valdimarsdottir, Bryndis / Sigurdsson, Snaevar / Gudjonsson, Alexander / Halldorsson, Skarphedinn / Johannsson, Freyr / Rolfsson, Ottar / Lehmann, Fredrik / Ingthorsson, Saevar / Cherek, Paulina / Gudmundsson, Gudmundur H / Gardarsson, Fridrik R / Page, Clive P / Baldursson, Olafur / Gudjonsson, Thorarinn / Kricker, Jennifer A

    Respiratory research

    2019  Volume 20, Issue 1, Page(s) 129

    Abstract: Background: Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and reduction in exacerbation of chronic airway diseases. It is not clear whether the beneficial effects of Azm are due to its anti-microbial activity or other ... ...

    Abstract Background: Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and reduction in exacerbation of chronic airway diseases. It is not clear whether the beneficial effects of Azm are due to its anti-microbial activity or other pharmacological actions. We have shown that Azm affects the integrity of the bronchial epithelial barrier measured by increased transepithelial electrical resistance. To better understand these effects of Azm on bronchial epithelia we have investigated global changes in gene expression.
    Methods: VA10 bronchial epithelial cells were treated with Azm and cultivated in air-liquid interface conditions for up to 22 days. RNA was isolated at days 4, 10 and 22 and analyzed using high-throughput RNA sequencing. qPCR and immunostaining were used to confirm key findings from bioinformatic analyses. Detailed assessment of cellular changes was done using microscopy, followed by characterization of the lipidomic profiles of the multivesicular bodies present.
    Results: Bioinformatic analysis revealed that after 10 days of treatment genes encoding effectors of sterol and cholesterol metabolism were prominent. Interestingly, expression of genes associated with epidermal barrier differentiation, KRT1, CRNN, SPINK5 and DSG1, increased significantly at day 22. Together with immunostaining, these results suggest an epidermal differentiation pattern. We also found that Azm induced the formation of multivesicular and lamellar bodies in two different airway epithelial cell lines. Lipidomic analysis revealed that Azm was entrapped in multivesicular bodies linked to different types of lipids, most notably palmitate and stearate. Furthermore, targeted analysis of lipid species showed accumulation of phosphatidylcholines, as well as ceramide derivatives.
    Conclusions: Taken together, we demonstrate how Azm might confer its barrier enhancing effects, via activation of epidermal characteristics and changes to intracellular lipid dynamics. These effects of Azm could explain the unexpected clinical benefit observed during Azm-treatment of patients with various lung diseases affecting barrier function.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Azithromycin/pharmacology ; Cell Differentiation/drug effects ; Cell Differentiation/physiology ; Cell Line ; Epidermis/drug effects ; Epidermis/metabolism ; Humans ; Multivesicular Bodies/drug effects ; Multivesicular Bodies/metabolism ; Respiratory Mucosa/cytology ; Respiratory Mucosa/drug effects ; Respiratory Mucosa/metabolism
    Chemical Substances Anti-Bacterial Agents ; Azithromycin (83905-01-5)
    Language English
    Publishing date 2019-06-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041675-1
    ISSN 1465-993X ; 1465-9921
    ISSN (online) 1465-993X
    ISSN 1465-9921
    DOI 10.1186/s12931-019-1101-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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