Increase of γ-Fe<inf>2</inf>O<inf>3</inf>/CNT composite quantum capacitance by structural design for performance optimization of electrode materials
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05.05.2020 |
Shunaev V.V.
Ushakov A.V.
Glukhova O.E.
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International Journal of Quantum Chemistry |
10.1002/qua.26165 |
0 |
Ссылка
© 2020 Wiley Periodicals, Inc. Performance optimization of electrode materials for lithium-ion batteries is one the most important scientific problems. In this paper, we suggest structural design of γ-Fe2O3/CNT composite for increase of its quantum capacitance that is required by modern energy storage devices capable of quick transfer or accumulation of energy and ensuring long-term autonomous operation. For this goal, we investigate the specific quantum capacitance of the γ-Fe2O3/CNT composites with a different content of maghemite by quantum chemical methods. The content of maghemite is varied by length of CNTs as well as by number of γ-Fe2O3 unit cell the weight ratio equals 13.71%, 20.74%, 26.69%, and 34.30%. It is found that the quantum capacitance grows with increasing maghemite concentration. Calculations show that the value of QC at the Fermi level for γ-Fe2O3/CNT is correlated with the theoretical specific capacity of the material. Proposed in this work approach to calculating the quantum capacitance with further analysis of its dependence on voltage can be an effective tool for optimizing the content of the composite with the aim of balancing the Faradaic and non-Faradaic component of its functional activity.
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тезис
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Increase of γ-Fe<inf>2</inf>O<inf>3</inf>/CNT composite quantum capacitance by structural design for performance optimization of electrode materials
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05.05.2020 |
Shunaev V.V.
Ushakov A.V.
Glukhova O.E.
|
International Journal of Quantum Chemistry |
10.1002/qua.26165 |
0 |
Ссылка
© 2020 Wiley Periodicals, Inc. Performance optimization of electrode materials for lithium-ion batteries is one the most important scientific problems. In this paper, we suggest structural design of γ-Fe2O3/CNT composite for increase of its quantum capacitance that is required by modern energy storage devices capable of quick transfer or accumulation of energy and ensuring long-term autonomous operation. For this goal, we investigate the specific quantum capacitance of the γ-Fe2O3/CNT composites with a different content of maghemite by quantum chemical methods. The content of maghemite is varied by length of CNTs as well as by number of γ-Fe2O3 unit cell the weight ratio equals 13.71%, 20.74%, 26.69%, and 34.30%. It is found that the quantum capacitance grows with increasing maghemite concentration. Calculations show that the value of QC at the Fermi level for γ-Fe2O3/CNT is correlated with the theoretical specific capacity of the material. Proposed in this work approach to calculating the quantum capacitance with further analysis of its dependence on voltage can be an effective tool for optimizing the content of the composite with the aim of balancing the Faradaic and non-Faradaic component of its functional activity.
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тезис
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Modifications of addition poly(5-vinyl-2-norbornene) and gas-transport properties of the obtained polymers
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01.04.2020 |
Wozniak A.
Bermesheva E.
Andreyanov F.
Borisov I.
Zarezin D.
Bakhtin D.
Gavrilova N.
Ilyasov I.
Nechaev M.
Asachenko A.
Topchiy M.
Volkov A.
Finkelshtein E.
Ren X.
Bermeshev M.
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Reactive and Functional Polymers |
10.1016/j.reactfunctpolym.2020.104513 |
0 |
Ссылка
© 2020 Elsevier B.V. Herein four modified polymers were prepared from readily available addition poly(5-vinyl-2-norbornene) (PVNB) and their gas-transport properties were studied in detail. Hydrogenation, epoxidation, cyclopropanation and thiol-en reactions were chosen for the modifications of PVNB. Hydrogenation of PVNB was performed using p-toluenesulfonyl hydrazide. Epoxidation of PVNB was realized employing m-chloroperoxybenzoic acid. Cyclopropanation of PVNB was carried out using diazomethane in the presence of a Pd-catalyst. For thiol-en reaction, thioacetic acid was applied as the source of a thiol and AIBN as an initiator. All listed modifications were performed in high yields (≥80%) without the destruction of polymer main chains. The degree of functionalizations was up to 99%. The influence of these modifications on the properties of the resulting polymers was evaluated. Cyclopropanation and hydrogenation of PVNB led to an enhancement of gas permeability with minimal decrease in selectivity, while epoxidation or thioacetylation gave a substantial increase in CO2/N2 selectivity with decrease in permeability. The modified polymers with polar side-groups exhibited attractive selectivities for CO2/N2, CO2/CH4 and H2/N2 gas separations.
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тезис
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New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells
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01.03.2020 |
Faletrov Y.
Efimova V.
Horetski M.
Tugaeva K.
Frolova N.
Lin Q.
Isaeva L.
Rubtsov M.
Sluchanko N.
Novikova L.
Shkumatov V.
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Chemistry and Physics of Lipids |
10.1016/j.chemphyslip.2019.104850 |
0 |
Ссылка
© 2019 Elsevier B.V. 20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.g. Smoothened and yeast Osh4) and some other sterol-binding proteins (human LXRβ and STARD1; yeast START-kins Lam4S2 and Lam2S2). Having found good predicted membrane permeability and binding to some yeast proteins, we tested the compounds on microorganisms. Fluorescent microscopy indicated the uptake of the steroids by both Saccharomyces cerevisiae and Yarrowia lipolytica, whereas only S. cerevisiae demonstrated conversion of the compounds into 3-O-acetates, likely because 3-O-acetyltransferase Atf2p is present only in its genome. The new compounds provide new options to study the uptake, intracellular distribution and metabolism of sterols in yeast cells as well as might be used as ligands for sterol-binding proteins.
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тезис
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New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells
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01.03.2020 |
Faletrov Y.
Efimova V.
Horetski M.
Tugaeva K.
Frolova N.
Lin Q.
Isaeva L.
Rubtsov M.
Sluchanko N.
Novikova L.
Shkumatov V.
|
Chemistry and Physics of Lipids |
10.1016/j.chemphyslip.2019.104850 |
0 |
Ссылка
© 2019 Elsevier B.V. 20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.g. Smoothened and yeast Osh4) and some other sterol-binding proteins (human LXRβ and STARD1; yeast START-kins Lam4S2 and Lam2S2). Having found good predicted membrane permeability and binding to some yeast proteins, we tested the compounds on microorganisms. Fluorescent microscopy indicated the uptake of the steroids by both Saccharomyces cerevisiae and Yarrowia lipolytica, whereas only S. cerevisiae demonstrated conversion of the compounds into 3-O-acetates, likely because 3-O-acetyltransferase Atf2p is present only in its genome. The new compounds provide new options to study the uptake, intracellular distribution and metabolism of sterols in yeast cells as well as might be used as ligands for sterol-binding proteins.
Читать
тезис
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New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells
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01.03.2020 |
Faletrov Y.
Efimova V.
Horetski M.
Tugaeva K.
Frolova N.
Lin Q.
Isaeva L.
Rubtsov M.
Sluchanko N.
Novikova L.
Shkumatov V.
|
Chemistry and Physics of Lipids |
10.1016/j.chemphyslip.2019.104850 |
0 |
Ссылка
© 2019 Elsevier B.V. 20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.g. Smoothened and yeast Osh4) and some other sterol-binding proteins (human LXRβ and STARD1; yeast START-kins Lam4S2 and Lam2S2). Having found good predicted membrane permeability and binding to some yeast proteins, we tested the compounds on microorganisms. Fluorescent microscopy indicated the uptake of the steroids by both Saccharomyces cerevisiae and Yarrowia lipolytica, whereas only S. cerevisiae demonstrated conversion of the compounds into 3-O-acetates, likely because 3-O-acetyltransferase Atf2p is present only in its genome. The new compounds provide new options to study the uptake, intracellular distribution and metabolism of sterols in yeast cells as well as might be used as ligands for sterol-binding proteins.
Читать
тезис
|
New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells
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01.03.2020 |
Faletrov Y.
Efimova V.
Horetski M.
Tugaeva K.
Frolova N.
Lin Q.
Isaeva L.
Rubtsov M.
Sluchanko N.
Novikova L.
Shkumatov V.
|
Chemistry and Physics of Lipids |
10.1016/j.chemphyslip.2019.104850 |
0 |
Ссылка
© 2019 Elsevier B.V. 20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.g. Smoothened and yeast Osh4) and some other sterol-binding proteins (human LXRβ and STARD1; yeast START-kins Lam4S2 and Lam2S2). Having found good predicted membrane permeability and binding to some yeast proteins, we tested the compounds on microorganisms. Fluorescent microscopy indicated the uptake of the steroids by both Saccharomyces cerevisiae and Yarrowia lipolytica, whereas only S. cerevisiae demonstrated conversion of the compounds into 3-O-acetates, likely because 3-O-acetyltransferase Atf2p is present only in its genome. The new compounds provide new options to study the uptake, intracellular distribution and metabolism of sterols in yeast cells as well as might be used as ligands for sterol-binding proteins.
Читать
тезис
|
New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells
|
01.03.2020 |
Faletrov Y.
Efimova V.
Horetski M.
Tugaeva K.
Frolova N.
Lin Q.
Isaeva L.
Rubtsov M.
Sluchanko N.
Novikova L.
Shkumatov V.
|
Chemistry and Physics of Lipids |
10.1016/j.chemphyslip.2019.104850 |
0 |
Ссылка
© 2019 Elsevier B.V. 20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.g. Smoothened and yeast Osh4) and some other sterol-binding proteins (human LXRβ and STARD1; yeast START-kins Lam4S2 and Lam2S2). Having found good predicted membrane permeability and binding to some yeast proteins, we tested the compounds on microorganisms. Fluorescent microscopy indicated the uptake of the steroids by both Saccharomyces cerevisiae and Yarrowia lipolytica, whereas only S. cerevisiae demonstrated conversion of the compounds into 3-O-acetates, likely because 3-O-acetyltransferase Atf2p is present only in its genome. The new compounds provide new options to study the uptake, intracellular distribution and metabolism of sterols in yeast cells as well as might be used as ligands for sterol-binding proteins.
Читать
тезис
|
New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells
|
01.03.2020 |
Faletrov Y.
Efimova V.
Horetski M.
Tugaeva K.
Frolova N.
Lin Q.
Isaeva L.
Rubtsov M.
Sluchanko N.
Novikova L.
Shkumatov V.
|
Chemistry and Physics of Lipids |
10.1016/j.chemphyslip.2019.104850 |
0 |
Ссылка
© 2019 Elsevier B.V. 20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.g. Smoothened and yeast Osh4) and some other sterol-binding proteins (human LXRβ and STARD1; yeast START-kins Lam4S2 and Lam2S2). Having found good predicted membrane permeability and binding to some yeast proteins, we tested the compounds on microorganisms. Fluorescent microscopy indicated the uptake of the steroids by both Saccharomyces cerevisiae and Yarrowia lipolytica, whereas only S. cerevisiae demonstrated conversion of the compounds into 3-O-acetates, likely because 3-O-acetyltransferase Atf2p is present only in its genome. The new compounds provide new options to study the uptake, intracellular distribution and metabolism of sterols in yeast cells as well as might be used as ligands for sterol-binding proteins.
Читать
тезис
|
New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells
|
01.03.2020 |
Faletrov Y.
Efimova V.
Horetski M.
Tugaeva K.
Frolova N.
Lin Q.
Isaeva L.
Rubtsov M.
Sluchanko N.
Novikova L.
Shkumatov V.
|
Chemistry and Physics of Lipids |
10.1016/j.chemphyslip.2019.104850 |
0 |
Ссылка
© 2019 Elsevier B.V. 20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.g. Smoothened and yeast Osh4) and some other sterol-binding proteins (human LXRβ and STARD1; yeast START-kins Lam4S2 and Lam2S2). Having found good predicted membrane permeability and binding to some yeast proteins, we tested the compounds on microorganisms. Fluorescent microscopy indicated the uptake of the steroids by both Saccharomyces cerevisiae and Yarrowia lipolytica, whereas only S. cerevisiae demonstrated conversion of the compounds into 3-O-acetates, likely because 3-O-acetyltransferase Atf2p is present only in its genome. The new compounds provide new options to study the uptake, intracellular distribution and metabolism of sterols in yeast cells as well as might be used as ligands for sterol-binding proteins.
Читать
тезис
|
Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation
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01.02.2020 |
Petanidis S.
Domvri K.
Porpodis K.
Anestakis D.
Freitag L.
Hohenforst-Schmidt W.
Tsavlis D.
Zarogoulidis K.
|
Biomedicine and Pharmacotherapy |
10.1016/j.biopha.2019.109461 |
0 |
Ссылка
© 2019 The Authors Immunosuppressive chemoresistance is a major challenge in lung cancer treatment. Exosomes present in the tumor microenviroment are implicated in chemoresistant-related immune suppression, and metastasis but the exact pathogenic role of lung-derived exosomes is still uncertain. Recent reports reveal that lung cancer pathogenesis is strictly associated with a exosomal tumor supportive status and a dysfunctional immune system. In this study, we investigate the role of Kras-derived exosomes in chemoresistant immunosuppression in which neoplastic cells create a metabolic-sustained microenvironment. Findings reveal that Kras-derived exosomes induce regulation of SMARCE1/NCOR1 chromatin remodeling genes promoting pre-metastatic niche formation in naive mice and consequently increase lung metastatic burden. Furthermore, exosomal Kras inhibition downregulated transcription factor BACH2/GATA-3 expression in lung tumor tissues by shifting pyruvate/PKM2 dependent metabolism, contributing to a tumor-restraining status. Further co-treatment with carboplatin triggered RIP3/TNFa dependent necroptosis in ex vivo cells accompanied by differential expression of immunosuppressive miR-146/miR-210 regulators in metastatic lung cancer patients. Overall, these findings demonstrate the multifaceted roles of Kras-derived exosomes in sustaining lung immunosuppressive metastasis and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
Читать
тезис
|
Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation
|
01.02.2020 |
Petanidis S.
Domvri K.
Porpodis K.
Anestakis D.
Freitag L.
Hohenforst-Schmidt W.
Tsavlis D.
Zarogoulidis K.
|
Biomedicine and Pharmacotherapy |
10.1016/j.biopha.2019.109461 |
0 |
Ссылка
© 2019 The Authors Immunosuppressive chemoresistance is a major challenge in lung cancer treatment. Exosomes present in the tumor microenviroment are implicated in chemoresistant-related immune suppression, and metastasis but the exact pathogenic role of lung-derived exosomes is still uncertain. Recent reports reveal that lung cancer pathogenesis is strictly associated with a exosomal tumor supportive status and a dysfunctional immune system. In this study, we investigate the role of Kras-derived exosomes in chemoresistant immunosuppression in which neoplastic cells create a metabolic-sustained microenvironment. Findings reveal that Kras-derived exosomes induce regulation of SMARCE1/NCOR1 chromatin remodeling genes promoting pre-metastatic niche formation in naive mice and consequently increase lung metastatic burden. Furthermore, exosomal Kras inhibition downregulated transcription factor BACH2/GATA-3 expression in lung tumor tissues by shifting pyruvate/PKM2 dependent metabolism, contributing to a tumor-restraining status. Further co-treatment with carboplatin triggered RIP3/TNFa dependent necroptosis in ex vivo cells accompanied by differential expression of immunosuppressive miR-146/miR-210 regulators in metastatic lung cancer patients. Overall, these findings demonstrate the multifaceted roles of Kras-derived exosomes in sustaining lung immunosuppressive metastasis and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
Читать
тезис
|
Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation
|
01.02.2020 |
Petanidis S.
Domvri K.
Porpodis K.
Anestakis D.
Freitag L.
Hohenforst-Schmidt W.
Tsavlis D.
Zarogoulidis K.
|
Biomedicine and Pharmacotherapy |
10.1016/j.biopha.2019.109461 |
0 |
Ссылка
© 2019 The Authors Immunosuppressive chemoresistance is a major challenge in lung cancer treatment. Exosomes present in the tumor microenviroment are implicated in chemoresistant-related immune suppression, and metastasis but the exact pathogenic role of lung-derived exosomes is still uncertain. Recent reports reveal that lung cancer pathogenesis is strictly associated with a exosomal tumor supportive status and a dysfunctional immune system. In this study, we investigate the role of Kras-derived exosomes in chemoresistant immunosuppression in which neoplastic cells create a metabolic-sustained microenvironment. Findings reveal that Kras-derived exosomes induce regulation of SMARCE1/NCOR1 chromatin remodeling genes promoting pre-metastatic niche formation in naive mice and consequently increase lung metastatic burden. Furthermore, exosomal Kras inhibition downregulated transcription factor BACH2/GATA-3 expression in lung tumor tissues by shifting pyruvate/PKM2 dependent metabolism, contributing to a tumor-restraining status. Further co-treatment with carboplatin triggered RIP3/TNFa dependent necroptosis in ex vivo cells accompanied by differential expression of immunosuppressive miR-146/miR-210 regulators in metastatic lung cancer patients. Overall, these findings demonstrate the multifaceted roles of Kras-derived exosomes in sustaining lung immunosuppressive metastasis and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
Читать
тезис
|
Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation
|
01.02.2020 |
Petanidis S.
Domvri K.
Porpodis K.
Anestakis D.
Freitag L.
Hohenforst-Schmidt W.
Tsavlis D.
Zarogoulidis K.
|
Biomedicine and Pharmacotherapy |
10.1016/j.biopha.2019.109461 |
0 |
Ссылка
© 2019 The Authors Immunosuppressive chemoresistance is a major challenge in lung cancer treatment. Exosomes present in the tumor microenviroment are implicated in chemoresistant-related immune suppression, and metastasis but the exact pathogenic role of lung-derived exosomes is still uncertain. Recent reports reveal that lung cancer pathogenesis is strictly associated with a exosomal tumor supportive status and a dysfunctional immune system. In this study, we investigate the role of Kras-derived exosomes in chemoresistant immunosuppression in which neoplastic cells create a metabolic-sustained microenvironment. Findings reveal that Kras-derived exosomes induce regulation of SMARCE1/NCOR1 chromatin remodeling genes promoting pre-metastatic niche formation in naive mice and consequently increase lung metastatic burden. Furthermore, exosomal Kras inhibition downregulated transcription factor BACH2/GATA-3 expression in lung tumor tissues by shifting pyruvate/PKM2 dependent metabolism, contributing to a tumor-restraining status. Further co-treatment with carboplatin triggered RIP3/TNFa dependent necroptosis in ex vivo cells accompanied by differential expression of immunosuppressive miR-146/miR-210 regulators in metastatic lung cancer patients. Overall, these findings demonstrate the multifaceted roles of Kras-derived exosomes in sustaining lung immunosuppressive metastasis and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
Читать
тезис
|
Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation
|
01.02.2020 |
Petanidis S.
Domvri K.
Porpodis K.
Anestakis D.
Freitag L.
Hohenforst-Schmidt W.
Tsavlis D.
Zarogoulidis K.
|
Biomedicine and Pharmacotherapy |
10.1016/j.biopha.2019.109461 |
0 |
Ссылка
© 2019 The Authors Immunosuppressive chemoresistance is a major challenge in lung cancer treatment. Exosomes present in the tumor microenviroment are implicated in chemoresistant-related immune suppression, and metastasis but the exact pathogenic role of lung-derived exosomes is still uncertain. Recent reports reveal that lung cancer pathogenesis is strictly associated with a exosomal tumor supportive status and a dysfunctional immune system. In this study, we investigate the role of Kras-derived exosomes in chemoresistant immunosuppression in which neoplastic cells create a metabolic-sustained microenvironment. Findings reveal that Kras-derived exosomes induce regulation of SMARCE1/NCOR1 chromatin remodeling genes promoting pre-metastatic niche formation in naive mice and consequently increase lung metastatic burden. Furthermore, exosomal Kras inhibition downregulated transcription factor BACH2/GATA-3 expression in lung tumor tissues by shifting pyruvate/PKM2 dependent metabolism, contributing to a tumor-restraining status. Further co-treatment with carboplatin triggered RIP3/TNFa dependent necroptosis in ex vivo cells accompanied by differential expression of immunosuppressive miR-146/miR-210 regulators in metastatic lung cancer patients. Overall, these findings demonstrate the multifaceted roles of Kras-derived exosomes in sustaining lung immunosuppressive metastasis and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
Читать
тезис
|
Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation
|
01.02.2020 |
Petanidis S.
Domvri K.
Porpodis K.
Anestakis D.
Freitag L.
Hohenforst-Schmidt W.
Tsavlis D.
Zarogoulidis K.
|
Biomedicine and Pharmacotherapy |
10.1016/j.biopha.2019.109461 |
0 |
Ссылка
© 2019 The Authors Immunosuppressive chemoresistance is a major challenge in lung cancer treatment. Exosomes present in the tumor microenviroment are implicated in chemoresistant-related immune suppression, and metastasis but the exact pathogenic role of lung-derived exosomes is still uncertain. Recent reports reveal that lung cancer pathogenesis is strictly associated with a exosomal tumor supportive status and a dysfunctional immune system. In this study, we investigate the role of Kras-derived exosomes in chemoresistant immunosuppression in which neoplastic cells create a metabolic-sustained microenvironment. Findings reveal that Kras-derived exosomes induce regulation of SMARCE1/NCOR1 chromatin remodeling genes promoting pre-metastatic niche formation in naive mice and consequently increase lung metastatic burden. Furthermore, exosomal Kras inhibition downregulated transcription factor BACH2/GATA-3 expression in lung tumor tissues by shifting pyruvate/PKM2 dependent metabolism, contributing to a tumor-restraining status. Further co-treatment with carboplatin triggered RIP3/TNFa dependent necroptosis in ex vivo cells accompanied by differential expression of immunosuppressive miR-146/miR-210 regulators in metastatic lung cancer patients. Overall, these findings demonstrate the multifaceted roles of Kras-derived exosomes in sustaining lung immunosuppressive metastasis and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
Читать
тезис
|
Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation
|
01.02.2020 |
Petanidis S.
Domvri K.
Porpodis K.
Anestakis D.
Freitag L.
Hohenforst-Schmidt W.
Tsavlis D.
Zarogoulidis K.
|
Biomedicine and Pharmacotherapy |
10.1016/j.biopha.2019.109461 |
0 |
Ссылка
© 2019 The Authors Immunosuppressive chemoresistance is a major challenge in lung cancer treatment. Exosomes present in the tumor microenviroment are implicated in chemoresistant-related immune suppression, and metastasis but the exact pathogenic role of lung-derived exosomes is still uncertain. Recent reports reveal that lung cancer pathogenesis is strictly associated with a exosomal tumor supportive status and a dysfunctional immune system. In this study, we investigate the role of Kras-derived exosomes in chemoresistant immunosuppression in which neoplastic cells create a metabolic-sustained microenvironment. Findings reveal that Kras-derived exosomes induce regulation of SMARCE1/NCOR1 chromatin remodeling genes promoting pre-metastatic niche formation in naive mice and consequently increase lung metastatic burden. Furthermore, exosomal Kras inhibition downregulated transcription factor BACH2/GATA-3 expression in lung tumor tissues by shifting pyruvate/PKM2 dependent metabolism, contributing to a tumor-restraining status. Further co-treatment with carboplatin triggered RIP3/TNFa dependent necroptosis in ex vivo cells accompanied by differential expression of immunosuppressive miR-146/miR-210 regulators in metastatic lung cancer patients. Overall, these findings demonstrate the multifaceted roles of Kras-derived exosomes in sustaining lung immunosuppressive metastasis and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.
Читать
тезис
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Single and double mucosal microflap CO<inf>2</inf> laser “sliding” technique in the management of iatrogenic glottic web: anatomical and functional results
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01.12.2019 |
Carta F.
Mariani C.
Quartu D.
Gioia E.
Chuchueva N.
Puxeddu R.
|
European Archives of Oto-Rhino-Laryngology |
10.1007/s00405-019-05632-0 |
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© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: An anterior glottic web consists of the formation of a bridge of scar tissue covered by epithelium between the anterior free edges of the true vocal cords and represents one of the most common complications of laryngeal endoscopic surgery for tumors involving the anterior commissure. Endoscopic surgery is the therapy of choice, but simple section of the web is burdened by a high recurrence rate. Topical application of mitomycin C, intracordal stents, and the use of mucosal microflaps have been proposed to improve outcomes. We report our experience with the use of single and double mucosal microflaps (sliding technique) during the management of iatrogenic anterior glottic web (IAGW). Methods: From November 2010 to December 2018, 30 patients (29 males, 1 female, mean age 65 years, range 47–87 years) were observed for IAGW, and 11 of these patients (36.7%) required surgical treatment. The Voice Handicap Index (VHI) and the GRBAS were used for the perceptive evaluation of pre- and post-operative voice quality. Results: A reduction of the web length was observed in all cases, and we did not observe any residual web at the mid-third of the glottis. The mean post-operative VHI score decreased from 45 to 24, and the mean post-operative GRBAS values were reduced from 2.8, 2.4, 2.3, 2.1, and 1.1 to 1.9, 1.4, 1.3, 1.1, and 0, respectively. Conclusions: The microflap technique represents an effective and reproducible one-step procedure that, in expert hands, allows to obtain good anatomical and functional results in a high percentage of cases.
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Comparison of the urinary glucose excretion contributions of SGLT2 and SGLT1: A quantitative systems pharmacology analysis in healthy individuals and patients with type 2 diabetes treated with SGLT2 inhibitors
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01.12.2019 |
Yakovleva T.
Sokolov V.
Chu L.
Tang W.
Greasley P.
Peilot Sjögren H.
Johansson S.
Peskov K.
Helmlinger G.
Boulton D.
Penland R.
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Diabetes, Obesity and Metabolism |
10.1111/dom.13858 |
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© 2019 John Wiley & Sons Ltd Aim: To develop a quantitative drug-disease systems model to investigate the paradox that sodium-glucose co-transporter (SGLT)2 is responsible for >80% of proximal tubule glucose reabsorption, yet SGLT2 inhibitor treatment results in only 30% to 50% less reabsorption in patients with type 2 diabetes mellitus (T2DM). Materials and methods: A physiologically based four-compartment model of renal glucose filtration, reabsorption and excretion via SGLT1 and SGLT2 was developed as a system of ordinary differential equations using R/IQRtools. SGLT2 inhibitor pharmacokinetics and pharmacodynamics were estimated from published concentration-time profiles in plasma and urine and from urinary glucose excretion (UGE) in healthy people and people with T2DM. Results: The final model showed that higher renal glucose reabsorption in people with T2DM versus healthy people was associated with 54% and 28% greater transporter capacity for SGLT1 and SGLT2, respectively. Additionally, the analysis showed that UGE is highly dependent on mean plasma glucose and estimated glomerular filtration rate (eGFR) and that their consideration is critical for interpreting clinical UGE findings. Conclusions: Quantitative drug-disease system modelling revealed mechanistic differences in renal glucose reabsorption and UGE between healthy people and those with T2DM, and clearly showed that SGLT2 inhibition significantly increased glucose available to SGLT1 downstream in the tubule. Importantly, we found that the findings of lower than expected UGE with SGLT2 inhibition are explained by the shift to SGLT1, which recovered additional glucose (~30% of total).
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p62/SQSTM1 expression in canine mammary tumours: Evolutionary notes
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01.12.2019 |
Mariotti F.
Magi G.
Gavazza A.
Vincenzetti S.
Komissarov A.
Shneider A.
Venanzi F.
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Veterinary and Comparative Oncology |
10.1111/vco.12523 |
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© 2019 John Wiley & Sons Ltd Recent studies highlighted the role of autophagy as a cardinal regulatory system for homeostasis and cancer-related signalling pathways. In this context, the deregulated expression of p62 – Sequestosome1 (p62/SQSTM1) – a protein acting both as an autophagy receptor and signalling hub, has been associated with tumour development and chronic inflammation. Multiple clinical studies test drugs targeting autophagy, and even more research is on the way to clinical trials. However, no comparative investigations have been carried out to identify adequate preclinical models to assess p62-based medicine. In veterinary oncology the role of p62 in cancer-related pathways has been largely ignored. We compared p62 sequences in multiple organisms and found that canine p62 significantly diverges from the humans and from other animals sequences. Then, we chart by immunohistochemistry the expression levels of p62 in canine mammary tumours. A total of 66 tumours and 10 non-neoplastic mammary samples were examined. The expression of p62 was higher in normal tissue and adenomas than carcinomas, with lowest levels of p62 protein detected in high grade carcinomas. In all cases examined the tumour stroma appeared to be p62-negative. Taken together our results would suggest that in dogs the association between p62 expression and cancer cells overturns that reported in human breast carcinoma, where p62 accumulates in malignant cells as compared to normal epithelium. Thus, at least in canine mammary tumours, p62 should be not considered a tumour-rejection antigen for an anti-cancer immunotherapy.
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