International Journal of Molecular Sciences

Editorial

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4 pages, 168 KiB

Open AccessEditorial

Plasma Biology

by Akikazu Sakudo and Yoshihito Yagyu

Int. J. Mol. Sci. 2021, 22(11), 5441; https://doi.org/10.3390/ijms22115441 - 21 May 2021

Cited by 3 | Viewed by 2162

Abstract

It is now more than 90 years since Irving Langmuir used the technical term “plasma” to describe an ionized gas [...] Full article

(This article belongs to the Special Issue Plasma Biology)

Research

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14 pages, 48909 KiB

Open AccessArticle

Impact of Reactive Oxygen and Nitrogen Species Produced by Plasma on Mdm2–p53 Complex

by Pankaj Attri, Hirofumi Kurita, Kazunori Koga and Masaharu Shiratani

Int. J. Mol. Sci. 2021, 22(17), 9585; https://doi.org/10.3390/ijms22179585 - 3 Sep 2021

Cited by 7 | Viewed by 2048

Abstract

The study of protein–protein interactions is of great interest. Several early studies focused on the murine double minute 2 (Mdm2)–tumor suppressor protein p53 interactions. However, the effect of plasma treatment on Mdm2 and p53 is still absent from the literature. This study investigated [...] Read more.

The study of protein–protein interactions is of great interest. Several early studies focused on the murine double minute 2 (Mdm2)–tumor suppressor protein p53 interactions. However, the effect of plasma treatment on Mdm2 and p53 is still absent from the literature. This study investigated the structural changes in Mdm2, p53, and the Mdm2–p53 complex before and after possible plasma oxidation through molecular dynamic (MD) simulations. MD calculation revealed that the oxidized Mdm2 bounded or unbounded showed high flexibility that might increase the availability of tumor suppressor protein p53 in plasma-treated cells. This study provides insight into Mdm2 and p53 for a better understanding of plasma oncology. Full article

(This article belongs to the Special Issue Plasma Biology)

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35 pages, 7942 KiB

Open AccessArticle

The Quest to Quantify Selective and Synergistic Effects of Plasma for Cancer Treatment: Insights from Mathematical Modeling

by Charlotta Bengtson and Annemie Bogaerts

Int. J. Mol. Sci. 2021, 22(9), 5033; https://doi.org/10.3390/ijms22095033 - 10 May 2021

Cited by 4 | Viewed by 2634

Abstract

Cold atmospheric plasma (CAP) and plasma-treated liquids (PTLs) have recently become a promising option for cancer treatment, but the underlying mechanisms of the anti-cancer effect are still to a large extent unknown. Although hydrogen peroxide (

H_{2} O_{2}

) has been [...] Read more.

Cold atmospheric plasma (CAP) and plasma-treated liquids (PTLs) have recently become a promising option for cancer treatment, but the underlying mechanisms of the anti-cancer effect are still to a large extent unknown. Although hydrogen peroxide (

H_{2} O_{2}

) has been recognized as the major anti-cancer agent of PTL and may enable selectivity in a certain concentration regime, the co-existence of nitrite can create a synergistic effect. We develop a mathematical model to describe the key species and features of the cellular response toward PTL. From the numerical solutions, we define a number of dependent variables, which represent feasible measures to quantify cell susceptibility in terms of the

H_{2} O_{2}

membrane diffusion rate constant and the intracellular catalase concentration. For each of these dependent variables, we investigate the regimes of selective versus non-selective, and of synergistic versus non-synergistic effect to evaluate their potential role as a measure of cell susceptibility. Our results suggest that the maximal intracellular

H_{2} O_{2}

concentration, which in the selective regime is almost four times greater for the most susceptible cells compared to the most resistant cells, could be used to quantify the cell susceptibility toward exogenous

H_{2} O_{2}

. We believe our theoretical approach brings novelty to the field of plasma oncology, and more broadly, to the field of redox biology, by proposing new ways to quantify the selective and synergistic anti-cancer effect of PTL in terms of inherent cell features. Full article

(This article belongs to the Special Issue Plasma Biology)

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21 pages, 3247 KiB

Open AccessArticle

Multivariate Optimization of the FLC-dc-APGD-Based Reaction-Discharge System for Continuous Production of a Plasma-Activated Liquid of Defined Physicochemical and Anti-Phytopathogenic Properties

by Anna Dzimitrowicz, Piotr Jamroz, Pawel Pohl, Weronika Babinska, Dominik Terefinko, Wojciech Sledz and Agata Motyka-Pomagruk

Int. J. Mol. Sci. 2021, 22(9), 4813; https://doi.org/10.3390/ijms22094813 - 1 May 2021

Cited by 4 | Viewed by 2974

Abstract

To the present day, no efficient plant protection method against economically important bacterial phytopathogens from the Pectobacteriaceae family has been implemented into agricultural practice. In this view, we have performed a multivariate optimization of the operating parameters of the reaction-discharge system, employing direct [...] Read more.

To the present day, no efficient plant protection method against economically important bacterial phytopathogens from the Pectobacteriaceae family has been implemented into agricultural practice. In this view, we have performed a multivariate optimization of the operating parameters of the reaction-discharge system, employing direct current atmospheric pressure glow discharge, generated in contact with a flowing liquid cathode (FLC-dc-APGD), for the production of a plasma-activated liquid (PAL) of defined physicochemical and anti-phytopathogenic properties. As a result, the effect of the operating parameters on the conductivity of PAL acquired under these conditions was assessed. The revealed optimal operating conditions, under which the PAL of the highest conductivity was obtained, were as follows: flow rate of the solution equaled 2.0 mL min⁻¹, the discharge current was 30 mA, and the inorganic salt concentration (ammonium nitrate, NH₄NO₃) in the solution turned out to be 0.50% (m/w). The developed PAL exhibited bacteriostatic and bactericidal properties toward Dickeya solani IFB0099 and Pectobacterium atrosepticum IFB5103 strains, with minimal inhibitory and minimal bactericidal concentrations equaling 25%. After 24 h exposure to 25% PAL, 100% (1−2 × 10⁶) of D. solani and P. atrosepticum cells lost viability. We attributed the antibacterial properties of PAL to the presence of deeply penetrating, reactive oxygen and nitrogen species (RONS), which were, in this case, OH, O, O₃, H₂O₂, HO₂, NH, N₂, N₂⁺, NO₂⁻, NO₃⁻, and NH₄⁺. Putatively, the generated low-cost, eco-friendly, easy-to-store, and transport PAL, exhibiting the required antibacterial and physicochemical properties, may find numerous applications in the plant protection sector. Full article

(This article belongs to the Special Issue Plasma Biology)

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23 pages, 8026 KiB

Open AccessArticle

The Influence of Cold Atmospheric Pressure Plasma-Treated Media on the Cell Viability, Motility, and Induction of Apoptosis in Human Non-Metastatic (MCF7) and Metastatic (MDA-MB-231) Breast Cancer Cell Lines

by Dominik Terefinko, Anna Dzimitrowicz, Aleksandra Bielawska-Pohl, Aleksandra Klimczak, Pawel Pohl and Piotr Jamroz

Int. J. Mol. Sci. 2021, 22(8), 3855; https://doi.org/10.3390/ijms22083855 - 8 Apr 2021

Cited by 28 | Viewed by 3424

Abstract

Breast cancer remains the most common type of cancer, occurring in middle-aged women, and often leads to patients’ death. In this work, we applied a cold atmospheric pressure plasma (CAPP)-based reaction-discharge system, one that is unique in its class, for the production of [...] Read more.

Breast cancer remains the most common type of cancer, occurring in middle-aged women, and often leads to patients’ death. In this work, we applied a cold atmospheric pressure plasma (CAPP)-based reaction-discharge system, one that is unique in its class, for the production of CAPP-activated media (DMEM and Opti-MEM); it is intended for further uses in breast cancer treatment. To reach this aim, different volumes of DMEM or Opti-MEM were treated by CAPP. Prepared media were exposed to the CAPP treatment at seven different time intervals and examined in respect of their impact on cell viability and motility, and the induction of the apoptosis in human non-metastatic (MCF7) and metastatic (MDA-MB-231) breast cancer cell lines. As a control, the influence of CAPP-activated media on the viability and motility, and the type of the cell death of the non-cancerous human normal MCF10A cell line, was estimated. Additionally, qualitative and quantitative analyses of the reactive oxygen and nitrogen species (RONS), generated during the CAPP operation in contact with analyzed media, were performed. Based on the conducted research, it was found that 180 s (media activation time by CAPP) should be considered as the minimal toxic dose, which significantly decreases the cell viability and the migration of MDA-MB-231 cells, and also disturbs life processes of MCF7 cells. Finally, CAPP-activated media led to the apoptosis of analyzed cell lines, especially of the metastatic MDA-MB-231 cell line. Therefore, the application of the CAPP system may be potentially applied as a therapeutic strategy for the management of highly metastatic human breast cancer. Full article

(This article belongs to the Special Issue Plasma Biology)

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14 pages, 4537 KiB

Open AccessArticle

Argon Plasma Exposure Augments Costimulatory Ligands and Cytokine Release in Human Monocyte-Derived Dendritic Cells

by Sander Bekeschus, Dorothee Meyer, Kevin Arlt, Thomas von Woedtke, Lea Miebach, Eric Freund and Ramona Clemen

Int. J. Mol. Sci. 2021, 22(7), 3790; https://doi.org/10.3390/ijms22073790 - 6 Apr 2021

Cited by 15 | Viewed by 2847

Abstract

Cold physical plasma is a partially ionized gas expelling many reactive oxygen and nitrogen species (ROS/RNS). Several plasma devices have been licensed for medical use in dermatology, and recent experimental studies suggest their putative role in cancer treatment. In cancer therapies with an [...] Read more.

Cold physical plasma is a partially ionized gas expelling many reactive oxygen and nitrogen species (ROS/RNS). Several plasma devices have been licensed for medical use in dermatology, and recent experimental studies suggest their putative role in cancer treatment. In cancer therapies with an immunological dimension, successful antigen presentation and inflammation modulation is a key hallmark to elicit antitumor immunity. Dendritic cells (DCs) are critical for this task. However, the inflammatory consequences of DCs following plasma exposure are unknown. To this end, human monocyte-derived DCs (moDCs) were expanded from isolated human primary monocytes; exposed to plasma; and their metabolic activity, surface marker expression, and cytokine profiles were analyzed. As controls, hydrogen peroxide, hypochlorous acid, and peroxynitrite were used. Among all types of ROS/RNS-mediated treatments, plasma exposure exerted the most notable increase of activation markers at 24 h such as CD25, CD40, and CD83 known to be crucial for T cell costimulation. Moreover, the treatments increased interleukin (IL)-1α, IL-6, and IL-23. Altogether, this study suggests plasma treatment augmenting costimulatory ligand and cytokine expression in human moDCs, which might exert beneficial effects in the tumor microenvironment. Full article

(This article belongs to the Special Issue Plasma Biology)

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14 pages, 1746 KiB

Open AccessArticle

Acidified Nitrite Contributes to the Antitumor Effect of Cold Atmospheric Plasma on Melanoma Cells

by Tom Zimmermann, Lisa A. Gebhardt, Lucas Kreiss, Christin Schneider, Stephanie Arndt, Sigrid Karrer, Oliver Friedrich, Michael J. M. Fischer and Anja-Katrin Bosserhoff

Int. J. Mol. Sci. 2021, 22(7), 3757; https://doi.org/10.3390/ijms22073757 - 4 Apr 2021

Cited by 11 | Viewed by 3198

Abstract

Cold atmospheric plasma (CAP) is partially ionized gas near room temperature with previously reported antitumor effects. Despite extensive research and growing interest in this technology, active components and molecular mechanisms of CAP are not fully understood to date. We used Raman spectroscopy and [...] Read more.

Cold atmospheric plasma (CAP) is partially ionized gas near room temperature with previously reported antitumor effects. Despite extensive research and growing interest in this technology, active components and molecular mechanisms of CAP are not fully understood to date. We used Raman spectroscopy and colorimetric assays to determine elevated nitrite and nitrate levels after treatment with a MiniFlatPlaster CAP device. Previously, we demonstrated CAP-induced acidification. Cellular effects of nitrite and strong extracellular acidification were assessed using live-cell imaging of intracellular Ca²⁺ levels, cell viability analysis as well as quantification of p21 and DNA damage. We further characterized these observations by analyzing established molecular effects of CAP treatment. A synergistic effect of nitrite and acidification was found, leading to strong cytotoxicity in melanoma cells. Interestingly, protein nitration and membrane damage were absent after treatment with acidified nitrite, thereby challenging their contribution to CAP-induced cytotoxicity. Further, phosphorylation of ERK1/2 was increased after treatment with both acidified nitrite and indirect CAP. This study characterizes the impact of acidified nitrite on melanoma cells and supports the importance of RNS during CAP treatment. Further, it defines and evaluates important molecular mechanisms that are involved in the cancer cell response to CAP. Full article

(This article belongs to the Special Issue Plasma Biology)

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15 pages, 2278 KiB

Open AccessArticle

Genotypic and Phenotypic Changes in Candida albicans as a Result of Cold Plasma Treatment

by Ewa Tyczkowska-Sieroń, Tadeusz Kałużewski, Magdalena Grabiec, Bogdan Kałużewski and Jacek Tyczkowski

Int. J. Mol. Sci. 2020, 21(21), 8100; https://doi.org/10.3390/ijms21218100 - 30 Oct 2020

Cited by 8 | Viewed by 2240

Abstract

We treated Candida albicans cells with a sublethal dose of nonequilibrium (cold) atmospheric-pressure He plasma and studied alterations in the genome of this fungus as well as changes in the phenotypic traits, such as assimilation of carbon from carbohydrates, hydrolytic enzyme activity, and [...] Read more.

We treated Candida albicans cells with a sublethal dose of nonequilibrium (cold) atmospheric-pressure He plasma and studied alterations in the genome of this fungus as well as changes in the phenotypic traits, such as assimilation of carbon from carbohydrates, hydrolytic enzyme activity, and drug susceptibility. There is a general problem if we use cold plasma to kill microorganism cells and some of them survive the process—whether the genotypic and phenotypic features of the cells are significantly altered in this case, and, if so, whether these changes are environmentally hazardous. Our molecular genetic studies have identified six single nucleotide variants, six insertions, and five deletions, which are most likely significant changes after plasma treatment. It was also found that out of 19 tested hydrolytic enzymes, 10 revealed activity, of which nine temporarily decreased their activity and one (naphthol-AS-BI- phosphohydrolase) permanently increased activity as a result of the plasma treatment. In turn, carbon assimilation and drug susceptibility were not affected by plasma. Based on the performed studies, it can be concluded that the observed changes in C. albicans cells that survived the plasma action are not of significant importance to the environment, especially for the drug resistance and pathogenicity of this fungus. Full article

(This article belongs to the Special Issue Plasma Biology)

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16 pages, 2896 KiB

Open AccessArticle

Inhibition of Angiogenesis by Treatment with Cold Atmospheric Plasma as a Promising Therapeutic Approach in Oncology

by Lyubomir Haralambiev, Ole Neuffer, Andreas Nitsch, Nele C. Kross, Sander Bekeschus, Peter Hinz, Alexander Mustea, Axel Ekkernkamp, Denis Gümbel and Matthias B. Stope

Int. J. Mol. Sci. 2020, 21(19), 7098; https://doi.org/10.3390/ijms21197098 - 26 Sep 2020

Cited by 12 | Viewed by 2897

Abstract

Background: Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. [...] Read more.

Background: Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy and the patient’s further prognosis. Whether the CAP influences this process is unknown, and the first indications in this regard are addressed in this study. Methods: Two different devices, kINPen and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes, caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was performed to examine the capillary tube formation abilities of HDMEC and their migration was messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment, a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was performed. Results: The direct CAP treatment of the HDMEC showed a robust growth-inhibiting effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application. These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results were independent of the CAP device. Both the migration and tube formation of HDMEC were significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP treatment on a non-malignant cell line. Full article

(This article belongs to the Special Issue Plasma Biology)

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12 pages, 1753 KiB

Open AccessArticle

Antibiotic-Resistant and Non-Resistant Bacteria Display Similar Susceptibility to Dielectric Barrier Discharge Plasma

by Akikazu Sakudo and Tatsuya Misawa

Int. J. Mol. Sci. 2020, 21(17), 6326; https://doi.org/10.3390/ijms21176326 - 31 Aug 2020

Cited by 20 | Viewed by 3797

Abstract

Here, we examined whether antibiotic-resistant and non-resistant bacteria show a differential susceptibility to plasma treatment. Escherichia coli DH5α were transformed with pPRO-EX-HT-CAT, which encodes an ampicillin resistance gene and chloramphenicol acetyltransferase (CAT) gene, and then treated with a dielectric barrier discharge (DBD) plasma [...] Read more.

Here, we examined whether antibiotic-resistant and non-resistant bacteria show a differential susceptibility to plasma treatment. Escherichia coli DH5α were transformed with pPRO-EX-HT-CAT, which encodes an ampicillin resistance gene and chloramphenicol acetyltransferase (CAT) gene, and then treated with a dielectric barrier discharge (DBD) plasma torch. Plasma treatment reduced the viable cell count of E. coli after transformation/selection and further cultured in ampicillin-containing and ampicillin-free medium. However, there was no significant difference in viable cell count between the transformed and untransformed E. coli after 1 min- and 2 min-plasma treatment. Furthermore, the enzyme-linked immunosorbent assay (ELISA) and acetyltransferase activity assay showed that the CAT activity was reduced after plasma treatment in both transformed and selected E. coli grown in ampicillin-containing or ampicillin-free medium. Loss of lipopolysaccharide and DNA damage caused by plasma treatment were confirmed by a Limulus test and polymerase chain reaction, respectively. Taken together, these findings suggest the plasma acts to degrade components of the bacteria and is therefore unlikely to display a differential affect against antibiotic-resistant and non-resistant bacteria. Therefore, the plasma method may be useful in eliminating bacteria that are recalcitrant to conventional antibiotic therapy. Full article

(This article belongs to the Special Issue Plasma Biology)

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18 pages, 4325 KiB

Open AccessArticle

Enhanced Osteogenic Differentiation of Human Mesenchymal Stem Cells on Amine-Functionalized Titanium Using Humidified Ammonia Supplied Nonthermal Atmospheric Pressure Plasma

by Jae-Sung Kwon, Sung-Hwan Choi, Eun Ha Choi, Kwang-Mahn Kim and Paul K. Chu

Int. J. Mol. Sci. 2020, 21(17), 6085; https://doi.org/10.3390/ijms21176085 - 24 Aug 2020

Cited by 10 | Viewed by 3075

Abstract

The surface molecular chemistry, such as amine functionality, of biomaterials plays a crucial role in the osteogenic activity of relevant cells and tissues during hard tissue regeneration. Here, we examined the possibilities of creating amine functionalities on the surface of titanium by using [...] Read more.

The surface molecular chemistry, such as amine functionality, of biomaterials plays a crucial role in the osteogenic activity of relevant cells and tissues during hard tissue regeneration. Here, we examined the possibilities of creating amine functionalities on the surface of titanium by using the nonthermal atmospheric pressure plasma jet (NTAPPJ) method with humidified ammonia, and the effects on human mesenchymal stem cell (hMSC) were investigated. Titanium samples were subjected to NTAPPJ treatments using nitrogen (N-P), air (A-P), or humidified ammonia (NA-P) as the plasma gas, while control (C-P) samples were not subjected to plasma treatment. After plasma exposure, all treatment groups showed increased hydrophilicity and had more attached cells than the C-P. Among the plasma-treated samples, the A-P and NA-P showed surface oxygen functionalities and exhibited greater cell proliferation than the C-P and N-P. The NA-P additionally showed surface amine-related functionalities and exhibited a higher level of alkaline phosphatase activity and osteocalcin expression than the other samples. The results can be explained by increases in fibronectin absorption and focal adhesion kinase gene expression on the NA-P samples. These findings suggest that NTAPPJ technology with humidified ammonia as a gas source has clinical potential for hard tissue generation. Full article

(This article belongs to the Special Issue Plasma Biology)

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19 pages, 3946 KiB

Open AccessArticle

Non-Thermal Plasma Couples Oxidative Stress to TRAIL Sensitization through DR5 Upregulation

by Soon Young Hwang, Ngoc Hoan Nguyen, Tae Jung Kim, Youngsoo Lee, Mi Ae Kang and Jong-Soo Lee

Int. J. Mol. Sci. 2020, 21(15), 5302; https://doi.org/10.3390/ijms21155302 - 26 Jul 2020

Cited by 7 | Viewed by 2715

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells without affecting most normal cells. Despite being in clinical testing, novel strategies to induce TRAIL-mediated apoptosis are in need to overcome cancer cell unresponsiveness and resistance. Plasma-activated medium (PAM) markedly stimulates [...] Read more.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells without affecting most normal cells. Despite being in clinical testing, novel strategies to induce TRAIL-mediated apoptosis are in need to overcome cancer cell unresponsiveness and resistance. Plasma-activated medium (PAM) markedly stimulates reactive oxygen/nitrogen species (ROS/RNS)-dependent apoptosis in cancer cells. We investigate the capability of PAM and TRAIL (PAM/TRAIL) combination therapy to overcome TRAIL resistance and improve the anticancer efficacy of TRAIL. The combinatorial treatment of PAM and TRAIL shows synergistic effects on growth inhibition in TRAIL-resistant cancer cells via augmented apoptosis by two attributes. DR5 (TRAIL-R2) transcription by CHOP is upregulated in a PAM-generated ROS/RNS-dependent manner, and PAM itself upregulates PTEN expression mediated by suppression of miR-425 which is involved in Akt inactivation, leading to increased apoptosis induction. Treatment of cancer cell lines with the antioxidant N-acetylcysteine reduces the extent of membrane dysfunction and the expression of both CHOP-DR5 and miR-425-PTEN axes, attenuating PAM/TRAIL-induced cancer cell apoptosis. These data suggest that PAM/TRAIL treatment is a novel approach to sensitizing cancer cells to TRAIL-induced apoptosis and overcoming TRAIL resistance. PAM is a promising candidate for further investigations as a chemotherapeutic sensitizer in the treatment of cancer. Full article

(This article belongs to the Special Issue Plasma Biology)

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23 pages, 8279 KiB

Open AccessArticle

Positive Effect of Cold Atmospheric Nitrogen Plasma on the Behavior of Mesenchymal Stem Cells Cultured on a Bone Scaffold Containing Iron Oxide-Loaded Silica Nanoparticles Catalyst

by Agata Przekora, Maïté Audemar, Joanna Pawlat, Cristina Canal, Jean-Sébastien Thomann, Cédric Labay, Michal Wojcik, Michal Kwiatkowski, Piotr Terebun, Grazyna Ginalska, Sophie Hermans and David Duday

Int. J. Mol. Sci. 2020, 21(13), 4738; https://doi.org/10.3390/ijms21134738 - 3 Jul 2020

Cited by 16 | Viewed by 3735

Abstract

Low-temperature atmospheric pressure plasma was demonstrated to have an ability to generate different reactive oxygen and nitrogen species (RONS), showing wide biological actions. Within this study, mesoporous silica nanoparticles (NPs) and Fe_xO_y/NPs catalysts were produced and embedded in the [...] Read more.

Low-temperature atmospheric pressure plasma was demonstrated to have an ability to generate different reactive oxygen and nitrogen species (RONS), showing wide biological actions. Within this study, mesoporous silica nanoparticles (NPs) and Fe_xO_y/NPs catalysts were produced and embedded in the polysaccharide matrix of chitosan/curdlan/hydroxyapatite biomaterial. Then, basic physicochemical and structural characterization of the NPs and biomaterials was performed. The primary aim of this work was to evaluate the impact of the combined action of cold nitrogen plasma and the materials produced on proliferation and osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (ADSCs), which were seeded onto the bone scaffolds containing NPs or Fe_xO_y/NPs catalysts. Incorporation of catalysts into the structure of the biomaterial was expected to enhance the formation of plasma-induced RONS, thereby improving stem cell behavior. The results obtained clearly demonstrated that short-time (16s) exposure of ADSCs to nitrogen plasma accelerated proliferation of cells grown on the biomaterial containing Fe_xO_y/NPs catalysts and increased osteocalcin production by the cells cultured on the scaffold containing pure NPs. Plasma activation of Fe_xO_y/NPs-loaded biomaterial resulted in the formation of appropriate amounts of oxygen-based reactive species that had positive impact on stem cell proliferation and at the same time did not negatively affect their osteogenic differentiation. Therefore, plasma-activated Fe_xO_y/NPs-loaded biomaterial is characterized by improved biocompatibility and has great clinical potential to be used in regenerative medicine applications to improve bone healing process. Full article

(This article belongs to the Special Issue Plasma Biology)

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17 pages, 1773 KiB

Open AccessArticle

Large-Scale Image Analysis for Investigating Spatio-Temporal Changes in Nuclear DNA Damage Caused by Nitrogen Atmospheric Pressure Plasma Jets

by Xu Han, James Kapaldo, Yueying Liu, M. Sharon Stack, Elahe Alizadeh and Sylwia Ptasinska

Int. J. Mol. Sci. 2020, 21(11), 4127; https://doi.org/10.3390/ijms21114127 - 10 Jun 2020

Cited by 6 | Viewed by 3232

Abstract

The effective clinical application of atmospheric pressure plasma jet (APPJ) treatments requires a well-founded methodology that can describe the interactions between the plasma jet and a treated sample and the temporal and spatial changes that result from the treatment. In this study, we [...] Read more.

The effective clinical application of atmospheric pressure plasma jet (APPJ) treatments requires a well-founded methodology that can describe the interactions between the plasma jet and a treated sample and the temporal and spatial changes that result from the treatment. In this study, we developed a large-scale image analysis method to identify the cell-cycle stage and quantify damage to nuclear DNA in single cells. The method was then tested and used to examine spatio-temporal distributions of nuclear DNA damage in two cell lines from the same anatomic location, namely the oral cavity, after treatment with a nitrogen APPJ. One cell line was malignant, and the other, nonmalignant. The results showed that DNA damage in cancer cells was maximized at the plasma jet treatment region, where the APPJ directly contacted the sample, and declined radially outward. As incubation continued, DNA damage in cancer cells decreased slightly over the first 4 h before rapidly decreasing by approximately 60% at 8 h post-treatment. In nonmalignant cells, no damage was observed within 1 h after treatment, but damage was detected 2 h after treatment. Notably, the damage was 5-fold less than that detected in irradiated cancer cells. Moreover, examining damage with respect to the cell cycle showed that S phase cells were more susceptible to DNA damage than either G1 or G2 phase cells. The proposed methodology for large-scale image analysis is not limited to APPJ post-treatment applications and can be utilized to evaluate biological samples affected by any type of radiation, and, more so, the cell-cycle classification can be used on any cell type with any nuclear DNA staining. Full article

(This article belongs to the Special Issue Plasma Biology)

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17 pages, 1872 KiB

Open AccessArticle

Cold Atmospheric Plasma and Silymarin Nanoemulsion Activate Autophagy in Human Melanoma Cells

by Manish Adhikari, Bhawana Adhikari, Bhagirath Ghimire, Sanjula Baboota and Eun Ha Choi

Int. J. Mol. Sci. 2020, 21(6), 1939; https://doi.org/10.3390/ijms21061939 - 12 Mar 2020

Cited by 45 | Viewed by 4293

Abstract

Background: Autophagy is reported as a survival or death-promoting pathway that is highly debatable in different kinds of cancer. Here, we examined the co-effect of cold atmospheric plasma (CAP) and silymarin nanoemulsion (SN) treatment on G-361 human melanoma cells via autophagy induction. Methods: [...] Read more.

Background: Autophagy is reported as a survival or death-promoting pathway that is highly debatable in different kinds of cancer. Here, we examined the co-effect of cold atmospheric plasma (CAP) and silymarin nanoemulsion (SN) treatment on G-361 human melanoma cells via autophagy induction. Methods: The temperature and pH of the media, along with the cell number, were evaluated. The intracellular glucose level and PI3K/mTOR and EGFR downstream pathways were assessed. Autophagy-related genes, related transcriptional factors, and autophagy induction were estimated using confocal microscopy, flow cytometry, and ELISA. Results: CAP treatment increased the temperature and pH of the media, while its combination with SN resulted in a decrease in intracellular ATP with the downregulation of PI3K/AKT/mTOR survival and RAS/MEK transcriptional pathways. Co-treatment blocked downstream paths of survival pathways and reduced PI3K (2 times), mTOR (10 times), EGFR (5 times), HRAS (5 times), and MEK (10 times). CAP and SN co-treated treatment modulates transcriptional factor expressions (ZKSCAN3, TFEB, FOXO1, CRTC2, and CREBBP) and specific genes (BECN-1, AMBRA-1, MAP1LC3A, and SQSTM) related to autophagy induction. Conclusion: CAP and SN together activate autophagy in G-361 cells by activating PI3K/mTOR and EGFR pathways, expressing autophagy-related transcription factors and genes. Full article

(This article belongs to the Special Issue Plasma Biology)

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22 pages, 6110 KiB

Open AccessArticle

Effects of Cold Jet Atmospheric Pressure Plasma on the Structural Characteristics and Immunoreactivity of Celiac-Toxic Peptides and Wheat Storage Proteins

by Fusheng Sun, Xiaoxue Xie, Yufan Zhang, Jiangwei Duan, Mingyu Ma, Yaqiong Wang, Ding Qiu, Xinpei Lu, Guangxiao Yang and Guangyuan He

Int. J. Mol. Sci. 2020, 21(3), 1012; https://doi.org/10.3390/ijms21031012 - 4 Feb 2020

Cited by 13 | Viewed by 3404

Abstract

The present research reported the effects of structural properties and immunoreactivity of celiac-toxic peptides and wheat storage proteins modified by cold jet atmospheric pressure (CJAP) plasma. It could generate numerous high-energy excited atoms, photons, electrons, and reactive oxygen and nitrogen species, including O [...] Read more.

The present research reported the effects of structural properties and immunoreactivity of celiac-toxic peptides and wheat storage proteins modified by cold jet atmospheric pressure (CJAP) plasma. It could generate numerous high-energy excited atoms, photons, electrons, and reactive oxygen and nitrogen species, including O₃, H₂O₂, •OH, NO₂⁻ and NO₃⁻ etc., to modify two model peptides and wheat storage proteins. The Orbitrap HR-LC-MS/MS was utilized to identify and quantify CJAP plasma-modified model peptide products. Backbone cleavage of QQPFP and PQPQLPY at specific proline and glutamine residues, accompanied by hydroxylation at the aromatic ring of phenylalanine and tyrosine residues, contributed to the reduction and modification of celiac-toxic peptides. Apart from fragmentation, oxidation, and agglomeration states were evaluated, including carbonyl formation and the decline of γ-gliadin. The immunoreactivity of gliadin extract declined over time, demonstrating a significant decrease by 51.95% after 60 min of CJAP plasma treatment in vitro. The CJAP plasma could initiate depolymerization of gluten polymer, thereby reducing the amounts of large-sized polymers. In conclusion, CJAP plasma could be employed as a potential technique in the modification and reduction of celiac-toxic peptides and wheat storage proteins. Full article

(This article belongs to the Special Issue Plasma Biology)

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Review

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23 pages, 8126 KiB

Open AccessReview

Insight on Solution Plasma in Aqueous Solution and Their Application in Modification of Chitin and Chitosan

by Chayanaphat Chokradjaroen, Jiangqi Niu, Gasidit Panomsuwan and Nagahiro Saito

Int. J. Mol. Sci. 2021, 22(9), 4308; https://doi.org/10.3390/ijms22094308 - 21 Apr 2021

Cited by 16 | Viewed by 3790

Abstract

Sustainability and environmental concerns have persuaded researchers to explore renewable materials, such as nature-derived polysaccharides, and add value by changing chemical structures with the aim to possess specific properties, like biological properties. Meanwhile, finding methods and strategies that can lower hazardous chemicals, simplify [...] Read more.

Sustainability and environmental concerns have persuaded researchers to explore renewable materials, such as nature-derived polysaccharides, and add value by changing chemical structures with the aim to possess specific properties, like biological properties. Meanwhile, finding methods and strategies that can lower hazardous chemicals, simplify production steps, reduce time consumption, and acquire high-purified products is an important task that requires attention. To break through these issues, electrical discharging in aqueous solutions at atmospheric pressure and room temperature, referred to as the “solution plasma process”, has been introduced as a novel process for modification of nature-derived polysaccharides like chitin and chitosan. This review reveals insight into the electrical discharge in aqueous solutions and scientific progress on their application in a modification of chitin and chitosan, including degradation and deacetylation. The influencing parameters in the plasma process are intensively explained in order to provide a guideline for the modification of not only chitin and chitosan but also other nature-derived polysaccharides, aiming to address economic aspects and environmental concerns. Full article

(This article belongs to the Special Issue Plasma Biology)

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44 pages, 929 KiB

Open AccessReview

Cold Atmospheric Pressure Plasma (CAP) as a New Tool for the Management of Vulva Cancer and Vulvar Premalignant Lesions in Gynaecological Oncology

by Pavol Zubor, Yun Wang, Alena Liskova, Marek Samec, Lenka Koklesova, Zuzana Dankova, Anne Dørum, Karol Kajo, Dana Dvorska, Vincent Lucansky, Bibiana Malicherova, Ivana Kasubova, Jan Bujnak, Milos Mlyncek, Carlos Alberto Dussan, Peter Kubatka, Dietrich Büsselberg and Olga Golubnitschaja

Int. J. Mol. Sci. 2020, 21(21), 7988; https://doi.org/10.3390/ijms21217988 - 27 Oct 2020

Cited by 17 | Viewed by 4984

Abstract

Vulvar cancer (VC) is a specific form of malignancy accounting for 5–6% of all gynaecologic malignancies. Although VC occurs most commonly in women after 60 years of age, disease incidence has risen progressively in premenopausal women in recent decades. VC demonstrates particular features [...] Read more.

Vulvar cancer (VC) is a specific form of malignancy accounting for 5–6% of all gynaecologic malignancies. Although VC occurs most commonly in women after 60 years of age, disease incidence has risen progressively in premenopausal women in recent decades. VC demonstrates particular features requiring well-adapted therapeutic approaches to avoid potential treatment-related complications. Significant improvements in disease-free survival and overall survival rates for patients diagnosed with post-stage I disease have been achieved by implementing a combination therapy consisting of radical surgical resection, systemic chemotherapy and/or radiotherapy. Achieving local control remains challenging. However, mostly due to specific anatomical conditions, the need for comprehensive surgical reconstruction and frequent post-operative healing complications. Novel therapeutic tools better adapted to VC particularities are essential for improving individual outcomes. To this end, cold atmospheric plasma (CAP) treatment is a promising option for VC, and is particularly appropriate for the local treatment of dysplastic lesions, early intraepithelial cancer, and invasive tumours. In addition, CAP also helps reduce inflammatory complications and improve wound healing. The application of CAP may realise either directly or indirectly utilising nanoparticle technologies. CAP has demonstrated remarkable treatment benefits for several malignant conditions, and has created new medical fields, such as “plasma medicine” and “plasma oncology”. This article highlights the benefits of CAP for the treatment of VC, VC pre-stages, and postsurgical wound complications. There has not yet been a published report of CAP on vulvar cancer cells, and so this review summarises the progress made in gynaecological oncology and in other cancers, and promotes an important, understudied area for future research. The paradigm shift from reactive to predictive, preventive and personalised medical approaches in overall VC management is also considered. Full article

(This article belongs to the Special Issue Plasma Biology)

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25 pages, 439 KiB

Open AccessReview

Cold Atmospheric Plasma: A Powerful Tool for Modern Medicine

by Dušan Braný, Dana Dvorská, Erika Halašová and Henrieta Škovierová

Int. J. Mol. Sci. 2020, 21(8), 2932; https://doi.org/10.3390/ijms21082932 - 22 Apr 2020

Cited by 203 | Viewed by 13644

Abstract

Cold atmospheric plasma use in clinical studies is mainly limited to the treatment of chronic wounds, but its application in a wide range of medical fields is now the goal of many analyses. It is therefore likely that its application spectrum will be [...] Read more.

Cold atmospheric plasma use in clinical studies is mainly limited to the treatment of chronic wounds, but its application in a wide range of medical fields is now the goal of many analyses. It is therefore likely that its application spectrum will be expanded in the future. Cold atmospheric plasma has been shown to reduce microbial load without any known significant negative effects on healthy tissues, and this should enhance its possible application to any microbial infection site. It has also been shown to have anti-tumour effects. In addition, it acts proliferatively on stem cells and other cultivated cells, and the highly increased nitric oxide levels have a very important effect on this proliferation. Cold atmospheric plasma use may also have a beneficial effect on immunotherapy in cancer patients. Finally, it is possible that the use of plasma devices will not remain limited to surface structures, because current endeavours to develop sufficiently miniature microplasma devices could very likely lead to its application in subcutaneous and internal structures. This study summarises the available literature on cold plasma action mechanisms and analyses of its current in vivo and in vitro use, primarily in the fields of regenerative and dental medicine and oncology. Full article

(This article belongs to the Special Issue Plasma Biology)

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