scholarly journals Possible Mechanism of Glucose Uptake Enhanced by Cold Atmospheric Plasma: Atomic Scale Simulations

Plasma ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 119-125 ◽  
Author(s):  
Jamoliddin Razzokov ◽  
Maksudbek Yusupov ◽  
Annemie Bogaerts

Cold atmospheric plasma (CAP) has shown its potential in biomedical applications, such as wound healing, cancer treatment and bacterial disinfection. Recent experiments have provided evidence that CAP can also enhance the intracellular uptake of glucose molecules which is important in diabetes therapy. In this respect, it is essential to understand the underlying mechanisms of intracellular glucose uptake induced by CAP, which is still unclear. Hence, in this study we try to elucidate the possible mechanism of glucose uptake by cells by performing computer simulations. Specifically, we study the transport of glucose molecules through native and oxidized membranes. Our simulation results show that the free energy barrier for the permeation of glucose molecules across the membrane decreases upon increasing the degree of oxidized lipids in the membrane. This indicates that the glucose permeation rate into cells increases when the CAP oxidation level in the cell membrane is increased.

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 249
Author(s):  
Zhitong Chen ◽  
Richard Obenchain ◽  
Richard E. Wirz

Conventional plasma jets for biomedical applications tend to have several drawbacks, such as high voltages, high gas delivery, large plasma probe volume, and the formation of discharge within the organ. Therefore, it is challenging to employ these jets inside a living organism’s body. Thus, we developed a single-electrode tiny plasma jet and evaluated its use for clinical biomedical applications. We investigated the effect of voltage input and flow rate on the jet length and studied the physical parameters of the plasma jet, including discharge voltage, average gas and subject temperature, and optical emissions via spectroscopy (OES). The interactions between the tiny plasma jet and five subjects (de-ionized (DI) water, metal, cardboard, pork belly, and pork muscle) were studied at distances of 10 mm and 15 mm from the jet nozzle. The results showed that the tiny plasma jet caused no damage or burning of tissues, and the ROS/RNS (reactive oxygen/nitrogen species) intensity increased when the distance was lowered from 15 mm to 10 mm. These initial observations establish the tiny plasma jet device as a potentially useful tool in clinical biomedical applications.


Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1038
Author(s):  
Haodong Cui ◽  
Min Jiang ◽  
Wenhua Zhou ◽  
Ming Gao ◽  
Rui He ◽  
...  

A carrier-free CRISPR/Cas9 ribonucleoprotein delivery strategy for genome editing mediated by a cold atmospheric plasma (CAP) is described. The CAP is promising in many biomedical applications due to efficient production of bioactive ionized species. The MCF-7 cancer cells after CAP exposure exhibit increased extracellular reactive oxygen and nitrogen species (RONS) and altered membrane potential and permeability. Hence, transmembrane transport of Ca2+ into the cells increases and accelerates ATP hydrolysis, resulting in enhanced ATP-dependent endocytosis. Afterwards, the increased Ca2+ and ATP contents promote the release of cargo into cytoplasm due to the enhanced endosomal escape. The increased membrane permeability also facilitates passive diffusion of foreign species across the membrane into the cytosol. After CAP exposure, the MCF-7 cells incubated with Cas9 ribonucleoprotein (Cas9-sgRNA complex, Cas9sg) with a size of about 15 nm show 88.9% uptake efficiency and 65.9% nuclear import efficiency via passive diffusion and ATP-dependent endocytosis pathways. The efficient transportation of active Cas9sg after the CAP treatment leads to 21.7% and 30.2% indel efficiencies in HEK293T and MCF-7 cells, respectively. This CAP-mediated transportation process provides a simple and robust alternative for the delivery of active CRISPR/Cas9 ribonucleoprotein. Additionally, the technique can be extended to other macro-biomolecules and nanomaterials to cater to different biomedical applications.


RSC Advances ◽  
2016 ◽  
Vol 6 (82) ◽  
pp. 78457-78467 ◽  
Author(s):  
Fanny Girard ◽  
Vasilica Badets ◽  
Sylvie Blanc ◽  
Kristaq Gazeli ◽  
Laurent Marlin ◽  
...  

Cold Atmospheric Plasmas (CAPs) are increasingly used for biomedical applications, their various reactive components must be then better determined. We demonstrate that peroxynitrite (ONOO−) is effectively a major reactive species generated by CAPs.


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1259
Author(s):  
Dayun Yan ◽  
Alisa Malyavko ◽  
Qihui Wang ◽  
Kostya (Ken) Ostrikov ◽  
Jonathan H. Sherman ◽  
...  

Cold atmospheric plasma (CAP) is a near-room-temperature, partially ionized gas composed of reactive neutral and charged species. CAP also generates physical factors, including ultraviolet (UV) radiation and thermal and electromagnetic (EM) effects. Studies over the past decade demonstrated that CAP could effectively induce death in a wide range of cell types, from mammalian to bacterial cells. Viruses can also be inactivated by a CAP treatment. The CAP-triggered cell-death types mainly include apoptosis, necrosis, and autophagy-associated cell death. Cell death and virus inactivation triggered by CAP are the foundation of the emerging medical applications of CAP, including cancer therapy, sterilization, and wound healing. Here, we systematically analyze the entire picture of multi-modal biological destruction by CAP treatment and their underlying mechanisms based on the latest discoveries particularly the physical effects on cancer cells.


2020 ◽  
Vol 21 (6) ◽  
pp. 1939 ◽  
Author(s):  
Manish Adhikari ◽  
Bhawana Adhikari ◽  
Bhagirath Ghimire ◽  
Sanjula Baboota ◽  
Eun Ha Choi

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.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Maksudbek Yusupov ◽  
Jamoliddin Razzokov ◽  
Rodrigo M. Cordeiro ◽  
Annemie Bogaerts

Aquaporins (AQPs) are transmembrane proteins that conduct not only water molecules across the cell membrane but also other solutes, such as reactive oxygen and nitrogen species (RONS), produced (among others) by cold atmospheric plasma (CAP). These RONS may induce oxidative stress in the cell interior, which plays a role in cancer treatment. The underlying mechanisms of the transport of RONS across AQPs, however, still remain obscure. We apply molecular dynamics simulations to investigate the permeation of both hydrophilic (H2O2 and OH) and hydrophobic (NO2 and NO) RONS through AQP1. Our simulations show that these RONS can all penetrate across the pores of AQP1. The permeation free energy barrier of OH and NO is lower than that of H2O2 and NO2, indicating that these radicals may have easier access to the pore interior and interact with the amino acid residues of AQP1. We also study the effect of RONS-induced oxidation of both the phospholipids and AQP1 (i.e., sulfenylation of Cys191) on the transport of the above-mentioned RONS across AQP1. Both lipid and protein oxidation seem to slightly increase the free energy barrier for H2O2 and NO2 permeation, while for OH and NO, we do not observe a strong effect of oxidation. The simulation results help to gain insight in the underlying mechanisms of the noticeable rise of CAP-induced RONS in cancer cells, thereby improving our understanding on the role of AQPs in the selective anticancer capacity of CAP.


2018 ◽  
Vol 18 (6) ◽  
pp. 784-804 ◽  
Author(s):  
Georg Bauer

Background: Application of cold atmospheric plasma to medium generates “plasma-activated medium” that induces apoptosis selectively in tumor cells and that has an antitumor effect in vivo. The underlying mechanisms are not well understood. Objective: Elucidation of potential chemical interactions within plasma-activated medium and of reactions of medium components with specific target structures of tumor cells should allow to define the active principle in plasma activated medium. Methods: Established knowledge of intercellular apoptosis-inducing reactive oxygen/nitrogen species-dependent signaling and its control by membrane-associated catalase and SOD was reviewed. Model experiments using extracellular singlet oxygen were analyzed with respect to catalase inactivation and their relevance for the antitumor action of cold atmospheric plasma. Potential interactions of this tumor cell-specific control system with components of plasma-activated medium or its reaction products were discussed within the scope of the reviewed signaling principles. Results: None of the long-lived species found in plasma-activated medium, such as nitrite and H2O2, nor OCl- or .NO seemed to have the potential to interfere with catalase-dependent control of apoptosis-inducing signaling of tumor cells when acting alone. However, the combination of H2O2 and nitrite might generate peroxynitrite. The protonation of peroxnitrite to peroxynitrous acid allows for the generation of hydroxyl radicals that react with H2O2, leading to the formation of hydroperoxide radicals. These allow for singlet oxygen generation and inactivation of membrane-associated catalase through an autoamplificatory mechanism, followed by intercellular apoptosis-inducing signaling. Conclusion: Nitrite and H2O2 in plasma-activated medium establish singlet oxygen-dependent interference selectively with the control system of tumor cells.


2018 ◽  
Vol 18 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Michael Keidar

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.


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