Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities
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01.12.2021 |
Hassanzadeh A.
Rahman H.S.
Markov A.
Endjun J.J.
Zekiy A.O.
Chartrand M.S.
Beheshtkhoo N.
Kouhbanani M.A.J.
Marofi F.
Nikoo M.
Jarahian M.
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Stem Cell Research and Therapy |
10.1186/s13287-021-02378-7 |
0 |
Ссылка
Recently, mesenchymal stem/stromal cells (MSCs) and their widespread biomedical applications have attracted great consideration from the scientific community around the world. However, reports have shown that the main populations of the transplanted MSCs are trapped in the liver, spleen, and lung upon administration, highlighting the importance of the development of cell-free therapies. Concerning rising evidence suggesting that the beneficial effects of MSC therapy are closely linked to MSC-released components, predominantly MSC-derived exosomes, the development of an MSC-based cell-free approach is of paramount importance. The exosomes are nano-sized (30–100 nm) lipid bilayer membrane vesicles, which are typically released by MSCs and are found in different body fluids. They include various bioactive molecules, such as messenger RNA (mRNA), microRNAs, proteins, and bioactive lipids, thus showing pronounced therapeutic competence for tissues recovery through the maintenance of their endogenous stem cells, the enhancement of regenerative phenotypic traits, inhibition of apoptosis concomitant with immune modulation, and stimulation of the angiogenesis. Conversely, the specific roles of MSC exosomes in the treatment of various tumors remain challenging. The development and clinical application of novel MSC-based cell-free strategies can be supported by better understanding their mechanisms, classifying the subpopulation of exosomes, enhancing the conditions of cell culture and isolation, and increasing the production of exosomes along with engineering exosomes to deliver drugs and therapeutic molecules to the target sites. In the current review, we deliver a brief overview of MSC-derived exosome biogenesis, composition, and isolation methods and discuss recent investigation regarding the therapeutic potential of MSC exosomes in regenerative medicine accompanied by their double-edged sword role in cancer.
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A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine
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01.12.2021 |
Moghadasi S.
Elveny M.
Rahman H.S.
Suksatan W.
Jalil A.T.
Abdelbasset W.K.
Yumashev A.V.
Shariatzadeh S.
Motavalli R.
Behzad F.
Marofi F.
Hassanzadeh A.
Pathak Y.
Jarahian M.
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Journal of Translational Medicine |
10.1186/s12967-021-02980-6 |
0 |
Ссылка
Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.
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тезис
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A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine
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01.12.2021 |
Moghadasi S.
Elveny M.
Rahman H.S.
Suksatan W.
Jalil A.T.
Abdelbasset W.K.
Yumashev A.V.
Shariatzadeh S.
Motavalli R.
Behzad F.
Marofi F.
Hassanzadeh A.
Pathak Y.
Jarahian M.
|
Journal of Translational Medicine |
10.1186/s12967-021-02980-6 |
0 |
Ссылка
Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.
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Parkinson's disease and pesticides: Are microRNAs the missing link?
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20.11.2020 |
Aloizou A.M.
Siokas V.
Sapouni E.M.
Sita N.
Liampas I.
Brotis A.G.
Rakitskii V.N.
Burykina T.I.
Aschner M.
Bogdanos D.P.
Tsatsakis A.
Hadjigeorgiou G.M.
Dardiotis E.
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Science of the Total Environment |
10.1016/j.scitotenv.2020.140591 |
0 |
Ссылка
© 2020 Elsevier B.V. Parkinson's disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and decline in the quality of life. It develops due to loss of dopaminergic neurons in the substantia nigra pars compacta, and among its pathogenic factors oxidative stress plays a critical role in disease progression. Pesticides are a broad class of chemicals widely used in agriculture and households for the protection of crops from insects and fungi. Several of them have been incriminated as risk factors for PD, but the underlying mechanisms have yet to be fully understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important role in regulating mRNA translation and protein synthesis. miRNA levels have been shown to be affected in several diseases as well. Since the studies on the association between pesticides and PD have yet to reach definitive conclusions, here we review recent evidence on deregulated microRNAs upon pesticide exposure, and attempt to find an overlap between miRNAs deregulated in PD and pesticides, as a missing link between the two, and enhance future research in this direction.
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тезис
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Antibacterial activity profile of miramistin in in vitro and in vivo models
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01.05.2020 |
Agafonova M.N.
Kazakova R.R.
Lubina A.P.
Zeldi M.I.
Nikitina E.V.
Balakin K.V.
Shtyrlin Y.G.
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Microbial Pathogenesis |
10.1016/j.micpath.2020.104072 |
0 |
Ссылка
© 2020 Background: Miramistin is a widely used antiseptic, disinfectant and preservative, and one of the most popular antimicrobial agents on pharmaceutical market of the Russian Federation ( http://www.dsm.ru/en/news/385/). However, there is a lack of reported systematic data on antibacterial efficacy of this agent obtained in accordance with the international standards. Aim: This paper represents a systematic study of antibacterial properties of miramistin. Another objective of this work is to evaluate and compare the exploratory performance of in vitro and in vivo protocols of antiseptics’ efficacy testing using miramistin as the reference antiseptic. Methods: Antibacterial activity of 0.1% and 0.2% aqueous solutions of miramistin against two museum strains of S. aureus (ATCC 209p) and E. coli (CDC F-50) was studied. Three standard in vitro laboratory tests (microdilution test, suspension test, and metal surface test), and one in vivo test (on rat's skin) were used. The study was conducted in accordance with the international regulatory documents. Results: Miramistin showed high bactericidal activity against the studied bacterial pathogens in the standard in vitro tests. Thus, in the microdilution test it showed expressed activity against S. aureus (MIC 8 μg/ml, MBC 16 μg/ml) and E. coli (MIC 32 μg/ml, MBC 128 μg/ml). In the suspension test, miramistin decreased the amount of colony forming units by at least 6 log10 units for S. aureus, and by at least 4.5 log10 units for E. coli. Transition to the metal surface test led to significant decrease of antibacterial activity by 1–3 log10 units as compared to the suspension test. Further dramatic reduction of antiseptic activity (by 3–4 log10 units) was observed in in vivo rat skin test. Addition of a protein contaminant (bovine serum albumin) led to a general decrease in the effectiveness of miramistin against the test pathogens (typically, by 1–2 log10 units). An interesting effect of exposure time-dependent reversal of miramistin's specificity to the studied Gram-positive S. aureus and the Gram-negative E. coli organisms was observed in the metal surface test. Conclusions: The results of this work provide systematic data on antibacterial efficacy of miramistin. They also underscore the need in relevant in vivo models for evaluation of antiseptics' efficacy. While the existing in vitro methods can be successfully applied at the discovery stages, it is necessary to use more realistic in vivo models at more advanced development stages. The observed selectivity reversal effect should be taken into account when carrying out the antiseptics’ efficacy testing and surface disinfection procedures.
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тезис
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Antibacterial activity profile of miramistin in in vitro and in vivo models
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01.05.2020 |
Agafonova M.N.
Kazakova R.R.
Lubina A.P.
Zeldi M.I.
Nikitina E.V.
Balakin K.V.
Shtyrlin Y.G.
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Microbial Pathogenesis |
10.1016/j.micpath.2020.104072 |
0 |
Ссылка
© 2020 Background: Miramistin is a widely used antiseptic, disinfectant and preservative, and one of the most popular antimicrobial agents on pharmaceutical market of the Russian Federation ( http://www.dsm.ru/en/news/385/). However, there is a lack of reported systematic data on antibacterial efficacy of this agent obtained in accordance with the international standards. Aim: This paper represents a systematic study of antibacterial properties of miramistin. Another objective of this work is to evaluate and compare the exploratory performance of in vitro and in vivo protocols of antiseptics’ efficacy testing using miramistin as the reference antiseptic. Methods: Antibacterial activity of 0.1% and 0.2% aqueous solutions of miramistin against two museum strains of S. aureus (ATCC 209p) and E. coli (CDC F-50) was studied. Three standard in vitro laboratory tests (microdilution test, suspension test, and metal surface test), and one in vivo test (on rat's skin) were used. The study was conducted in accordance with the international regulatory documents. Results: Miramistin showed high bactericidal activity against the studied bacterial pathogens in the standard in vitro tests. Thus, in the microdilution test it showed expressed activity against S. aureus (MIC 8 μg/ml, MBC 16 μg/ml) and E. coli (MIC 32 μg/ml, MBC 128 μg/ml). In the suspension test, miramistin decreased the amount of colony forming units by at least 6 log10 units for S. aureus, and by at least 4.5 log10 units for E. coli. Transition to the metal surface test led to significant decrease of antibacterial activity by 1–3 log10 units as compared to the suspension test. Further dramatic reduction of antiseptic activity (by 3–4 log10 units) was observed in in vivo rat skin test. Addition of a protein contaminant (bovine serum albumin) led to a general decrease in the effectiveness of miramistin against the test pathogens (typically, by 1–2 log10 units). An interesting effect of exposure time-dependent reversal of miramistin's specificity to the studied Gram-positive S. aureus and the Gram-negative E. coli organisms was observed in the metal surface test. Conclusions: The results of this work provide systematic data on antibacterial efficacy of miramistin. They also underscore the need in relevant in vivo models for evaluation of antiseptics' efficacy. While the existing in vitro methods can be successfully applied at the discovery stages, it is necessary to use more realistic in vivo models at more advanced development stages. The observed selectivity reversal effect should be taken into account when carrying out the antiseptics’ efficacy testing and surface disinfection procedures.
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тезис
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Antibacterial activity profile of miramistin in in vitro and in vivo models
|
01.05.2020 |
Agafonova M.N.
Kazakova R.R.
Lubina A.P.
Zeldi M.I.
Nikitina E.V.
Balakin K.V.
Shtyrlin Y.G.
|
Microbial Pathogenesis |
10.1016/j.micpath.2020.104072 |
0 |
Ссылка
© 2020 Background: Miramistin is a widely used antiseptic, disinfectant and preservative, and one of the most popular antimicrobial agents on pharmaceutical market of the Russian Federation ( http://www.dsm.ru/en/news/385/). However, there is a lack of reported systematic data on antibacterial efficacy of this agent obtained in accordance with the international standards. Aim: This paper represents a systematic study of antibacterial properties of miramistin. Another objective of this work is to evaluate and compare the exploratory performance of in vitro and in vivo protocols of antiseptics’ efficacy testing using miramistin as the reference antiseptic. Methods: Antibacterial activity of 0.1% and 0.2% aqueous solutions of miramistin against two museum strains of S. aureus (ATCC 209p) and E. coli (CDC F-50) was studied. Three standard in vitro laboratory tests (microdilution test, suspension test, and metal surface test), and one in vivo test (on rat's skin) were used. The study was conducted in accordance with the international regulatory documents. Results: Miramistin showed high bactericidal activity against the studied bacterial pathogens in the standard in vitro tests. Thus, in the microdilution test it showed expressed activity against S. aureus (MIC 8 μg/ml, MBC 16 μg/ml) and E. coli (MIC 32 μg/ml, MBC 128 μg/ml). In the suspension test, miramistin decreased the amount of colony forming units by at least 6 log10 units for S. aureus, and by at least 4.5 log10 units for E. coli. Transition to the metal surface test led to significant decrease of antibacterial activity by 1–3 log10 units as compared to the suspension test. Further dramatic reduction of antiseptic activity (by 3–4 log10 units) was observed in in vivo rat skin test. Addition of a protein contaminant (bovine serum albumin) led to a general decrease in the effectiveness of miramistin against the test pathogens (typically, by 1–2 log10 units). An interesting effect of exposure time-dependent reversal of miramistin's specificity to the studied Gram-positive S. aureus and the Gram-negative E. coli organisms was observed in the metal surface test. Conclusions: The results of this work provide systematic data on antibacterial efficacy of miramistin. They also underscore the need in relevant in vivo models for evaluation of antiseptics' efficacy. While the existing in vitro methods can be successfully applied at the discovery stages, it is necessary to use more realistic in vivo models at more advanced development stages. The observed selectivity reversal effect should be taken into account when carrying out the antiseptics’ efficacy testing and surface disinfection procedures.
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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.
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тезис
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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.
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тезис
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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.
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тезис
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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
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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.
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Data on occurrence of miRNA precursors in the Cucurbita maxima phloem sap
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01.02.2020 |
Tolstyko E.
Lezzhov A.
Solovieva A.
Solovyev A.
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Data in Brief |
10.1016/j.dib.2019.105083 |
0 |
Ссылка
© 2019 The Author(s) The phloem sieve elements (SEs), enucleate cells, contain RNAs, which are imported from surrounding tissues and cells, mostly companion cells tightly associated with SEs, and transported via the phloem over the whole plant body. The RNA phloem transport is essential for plant individual development and responses to environmental cues. Recently, we identified primary miRNA (pri-miRNA) sequences in de novo assembled transcriptome of Cucurbita maxima phloem sap and reported 11 most abundant pri-miRNAs [1]. Here, we provide the output of this analysis in complete detail. For the full set of pri-miRNAs identified in the C. maxima phloem sap transcriptome, data on relative abundance are provided along with annotated sequence data.
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Quantitation of Molecular Pathway Activation Using RNA Sequencing Data
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01.01.2020 |
Borisov N.
Sorokin M.
Garazha A.
Buzdin A.
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Methods in Molecular Biology |
10.1007/978-1-0716-0138-9_15 |
1 |
Ссылка
© Springer Science+Business Media, LLC, part of Springer Nature 2020. Intracellular molecular pathways (IMPs) control all major events in the living cell. IMPs are considered hotspots in biomedical sciences and thousands of IMPs have been discovered for humans and model organisms. Knowledge of IMPs activation is essential for understanding biological functions and differences between the biological objects at the molecular level. Here we describe the Oncobox system for accurate quantitative scoring activities of up to several thousand molecular pathways based on high throughput molecular data. Although initially designed for gene expression and mainly RNA sequencing data, Oncobox is now also applicable for quantitative proteomics, microRNA and transcription factor binding sites mapping data. The Oncobox system includes modules of gene expression data harmonization, aggregation and comparison and a recursive algorithm for automatic annotation of molecular pathways. The universal rationale of Oncobox enables scoring of signaling, metabolic, cytoskeleton, immunity, DNA repair, and other pathways in a multitude of biological objects. The Oncobox system can be helpful to all those working in the fields of genetics, biochemistry, interactomics, and big data analytics in molecular biomedicine.
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Development of composition and manufacturingmethod for combination drug product based onchitosan-containing pharmaceutical substances
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01.10.2018 |
Brkich L.
Pyatigorskaya N.
Brkich G.
Krasnyuk I.
Korol L.
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International Journal of Pharmaceutical Research |
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© 2018, Advanced Scientific Research. All rights reserved. The composition described in current article is based on derivatives of glucosamine and acrylate polymers and is intended for treatment of various infected wounds. A semi-transparent gel demonstrates complex therapeutic activity due to several active pharmaceutical ingredients (AFIs): chitosan, chymopsin, miramistin, and lidocaine hydrochloride. Mechanism of action of the developed drug is complex and includes several therapeutic effects: enzymatic biochemical wound debridement due to lysis of denaturated proteins (without healthy tissues damaging); indirect antimicrobial activity due to chymopsin that promotes lysis of microbial growth medium; direct antimicrobial effect is provided by miramistine; and the pain is reduced by lydocaine and intrinsic cooling effect of gel dosage form. Generalizing the literature data about the products used in the infected wounds treatment, the following AFIs were chosen for the development of the topical gel: complex of proteolytic agent chymopsin and chitosan, chitosan-miramistin complex, and lidocaine anesthetic. Hydroxypropyl methylcellulose, polyacrylamide, and glycerol were utilized as excipients. Proper development of vehicles for gels used in wound treatment can be justified by the necessity of soft action on the wound, required cooling effect, good release of AFIs from the matrix, and prevention of microbial growth.
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Role of miRNA in herpesvirus infections
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01.01.2018 |
Boichenko M.
Budanova E.
Sergeyev O.
Volchkova E.
Belaya O.
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Infektsionnye Bolezni |
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© 2018, Dynasty Publishing House. All rights reserved. This review analyzes the role of viral miRNAs produced by representatives of the Herpesviridae subfamilies (including Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae) in the development of herpesvirus infection. In all three subfamilies, microRNAs are involved in the regulation of latency, i.e. transition of lytic to latent infection. In CMV and HHV-8, miRNAs play an important role in escaping innate immunity. Moreover, viral miRNAs can be transferred to non-infected cells via exosomes.
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MicroRNA expression profile in patients in the early stages of ischemic stroke
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01.01.2018 |
Zhanin I.
Gusar V.
Timofeeva A.
Pinelis V.
Asanov A.
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Nevrologiya, Neiropsikhiatriya, Psikhosomatika |
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© Ima-Press Publishing House. All rights reserved. Stroke is one of the leading causes of death and disability in the population, has a complex multifactorial nature and develops through the interaction of environmental factors and genetic predisposition, the pattern and mechanisms of which have been insufficiently studied. Ischemic stroke (IS) is most commonly encountered. Objective: to investigate the differential expression of microRNAs (miRNAs) in the plasma of patients in the acute and subacute stages of stroke. Patients and methods. The investigation enrolled 10 patients (5 men and 5 women; mean age, 64.5 years) with IS and 10 gender- and age-matched volunteers (a control group). A real-time polymerase chain reaction (PCR) was used to analyze the expression of 45 miRNAs isolated from the plasma samples of the patients on days 1 and 8 after onset of IS and isolated once from those of the controls. Results. A list of 45 miRNAs, that might be potential biomarkers and/or prognostic factors of stroke, was compiled. The investigation showed a decrease in let-7i-3p and miR-23a-3p miRNA expression in patients on the first day after onset of IS compared to the control group. The expression of miR-23a-3p increased in the patients at 8 days after IS. The patients with IS and the controls both showed gender differences in the expression of let-7i-5p and miR-92b-3p. Conclusion. The in-silico analysis revealed specific miRNA clusters associated with the peculiarities of clinical manifestations of IS. This may suggest that the patients with the favorable and unfavorable course of stroke may have its different molecular basis. In addition, it is necessary to take into account gender differences in the expression of individual miRNAs in assessing their significance in the pathogenesis and prognosis of IS.
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Coding and non-coding: Molecular portrait of GIST and its clinical implication
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01.01.2018 |
Bure I.
Haller F.
Zaletaev D.
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Current Molecular Medicine |
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© 2018 Bentham Science Publishers. Gastrointestinal stromal tumours are the most common mesenchymal tumours of the gastrointestinal tract. Despite similar mutation pattern of activating mutations in KIT or PDGFRA receptors in 85% of cases, they demonstrate significantly heterogeneous clinical behaviour and pathological characteristics. This heterogeneity opens the question of the role of other factors and mechanisms of regulation in the development of GIST. Additional mutations in downstream effectors of GIST related signalling pathways or aberrant expression of non-coding RNAs may be additional contributing factors, the latter being increasingly recognized in carcinogenesis in general. Recently, a substantial progress has been achieved in understanding the functional roles of lncRNAs in GIST suggesting their potential employment as biomarkers and therapeutic targets in GIST. Moreover, some miRNAs have recently been found to be able to sensitize cells to imatinib, which could be an attractive option to overcome the resistance to the drug, which hampers the efficacy of GIST treatment. Therefore, the advantage can be taken of both coding and non-coding parts of the genome in order to significantly improve prognostication and help find personalized therapy for patients, depending on a subtype of GIST and personal characteristics.
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