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Cancer is a devastating and life-threatening disease. It is the second leading cause of death worldwide after heart diseases. While science has significantly advanced to improve the treatment outcome and quality of life in cancer patients, there are still many issues with the current therapies, such as toxicity and the development of resistance to treatment. Among the novel tools to overcome these limitations is nonthermal plasma (NTP) and its treatment regimens. Recent progress in NTP devices with ion temperatures close to room temperature demonstrated significant potential in cancer therapy. NTP devices provide a unique combination of reactive oxygen species (ROS), reactive nitrogen species (RNS), photons, and electric fields that exhibit desirable properties of triggering cell death pathways, selectively for cancer cells. While in principle NTP is nonnecrotic and gentle to the tissue, but reactive oxygen and nitrogen species (RONS)-triggered tumor cell death exhibited to have pro-immunogenic properties. Many in vitro and in vivo experiments have demonstrated antitumor effects of direct NTP, synergistic applications of NTP with anticancer drugs/treatments, and plasma-conditioned medium (PCM) applications against a variety of cancer cells. The latest results and findings in this field are the subject of this review along with a brief lay-reader-explanation of cancer and immunology. In this review, initially, we give an overview of the literature that deals with studies on the use of NTP for cancer treatment. Subsequently, we present typical results from that literature to illustrate the advances of NTP in oncology. Finally, we discuss some challenges and future scopes offered by NTP for cancer treatment. [ABSTRACT FROM AUTHOR]

Surgical incision infection of multidrug-resistant microorganisms (e.g., methicillin-resistant Staphylococcus aureus, MRSA) is a severe cause of poor wound healing, which is prevalent in healthcare facilities and constitutes a huge infectious disease burden in the world. The purpose of this study is to investigate the medical application and possible mechanisms of the cold atmospheric plasma jet on infected wounds. In this article, the New Zealand rabbit in vivo wound infected with MRSA is used as the wound healing animal model. The helium atmospheric-pressure dielectric-barrier-discharge (AP-DBD) plasma jet is employed to treat the wounds infected with MRSA. The wound healing, histological, and cytokine analyses are conducted to evaluate the efficacy of the helium AP-DBD plasma jet on the MRSA-infected wound healing process. The experimental results show that the helium AP-DBD plasma jet treatment on the wounds infected with MRSA can regulate the secretion of the cytokines, limit the inflammatory response and cell excessive proliferation, accelerate the process of re-epithelialization, and consequently, promote the wound healing process and the inactivation of the bacteria. [ABSTRACT FROM AUTHOR]

Chronic wounds are a major complication for diabetes mellitus (DM) patients, which cause discomfort and an increase in medical costs. The purpose of this study is to investigate the medical application and possible mechanisms of a cold atmospheric plasma jet in healing DM chronic wounds. In this paper, the genetic diabetic BKS.DB mice are used as the diabetic wound healing animal model, which have a stable glucose level and can avoid the effects or complications induced by surgical and chemical interventions. The helium atmospheric-pressure dielectric-barrier-discharge (AP-DBD) plasma jet is employed to treat the diabetic mice wounds with the fixed treatment time and distance of 15 s and 20.0 mm, respectively. The wound healing, histological, immunohistochemical, and cytokine analyses are conducted to evaluate the efficacy of the helium AP-DBD plasma jet on the chronic wound healing of the genetic diabetic mice. The experimental results show that the helium AP-DBD plasma jet treatment of wounds of genetic diabetic mice can regulate the secretion of transforming growth factor- $\beta $ (TGF- $\beta$) and fibroblast growth factors (FGFs), limit the inflammatory response and excessive cell proliferation, accelerate the process of re-epithelialization, and consequently, promote the chronic wound healing process. [ABSTRACT FROM AUTHOR]

A plasma jet enhanced oil-based drug, named plasma-activated oil (PAO) is produced in sunflower oil by a single-step, room temperature, energy-efficient, and environment-friendly dry plasma jet enabled process. Plasma jets with two different working gas combinations, argon + air and argon + O2, were generated, namely PAO (air) and PAO (O2), respectively. Several hours of plasma jet treatment substantially increased the hydrogen peroxide and carboxylic acid concentrations in the PAO. Although the electrophilic fatty acid nitroalkenes produced by nitric oxide and nitrite of the argon + air plasma jet increased the acid value of PAO (air), similar sterilization and wound healing effect suggest that PAO (air) and PAO (O2) have similar concentrations of hydrogen peroxide and carboxylic acid. PAO killed the common Gram-positive bacteria [methicillin-resistant staphylococcus aureus (MRSA) and Micrococcus luteus] and Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli) efficiently. PAO accelerated the healing of infected wounds by 33%. [ABSTRACT FROM AUTHOR]

The aim of this experiment is to enhance selected species in atmospheric pressure plasma jet (APPJ) that might be helpful for the wound healing purpose and to test the performance using basic diagnosis in plasma-treated liquid. A homemade APPJ device is driven by sinusoidal voltage with a excitation frequency of 25 kHz. Argon with admixture of small percentage of nitrogen, oxygen, and water vapor was selected to be carrier gas as the main sources of reactive species. Discharge power consumption is calculated by two approaches. Reactive oxygen species and reactive nitrogen species in the excited states are characterized by optical emission spectroscopy (OES). Excitation temperature $T_{\mathrm {exc}}$ in argon plasmas is calculated to estimate the electron energy distribution. The results show that argon plasmas with small addition of nitrogen and oxygen in this jet configuration are more efficient to generate desired reactive species in terms of OES diagnosis and liquid acidification. Moreover, the distinct efficiency of liquid acidification between direct and indirect plasma treatment of liquid has also been observed. [ABSTRACT FROM AUTHOR]

Plasma medicine is a rapidly advancing field. As one promising application, cold plasma has been ascribed a beneficial role in wound healing in which monocytes/macrophages play an important part. Wound healing and many other physiological and pathological processes are subject to redox control. Cold plasma expels reactive species of many kinds, thereby altering the redox state and mediating cell and tissue responses. Controlling this species efflux could be a valuable asset to control biological effects. We, therefore, investigated the biological response of a plasma treatment regimen that was gas shielded from the ambient environment. In this gas curtain, several N2:O2 ratios were investigated, and we discovered a modulation within the composition of active compounds (NO-2 , NO-3 , and H2O2) in physiological solutions. Using a human monocyte cell line, the cell's scavenging activity toward these molecules was assessed. With regard to cellular processes important in wound healing, such as cytokines release, O2 shielding provided stronger stimulation compared to N2 shielding. Altogether, the results support the idea that tuning the plasma-derived reactive species composition may be an interesting approach to improve plasma medical applications. [ABSTRACT FROM AUTHOR]

We evaluated a nonthermal plasma jet for a respective use to prevent infections from bacteria and yeasts. The plasma jet is generated from the flow of ambient air with 8 slm through a microhollow cathode discharge assembly that is operated with a direct current of 30 mA. With these parameters, the temperature in the jet reaches 43 ^\circ\C at 10 mm from the discharge. Agar plates that were inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Candida kefyr were treated at this distance, moving the plates through the jet in a meander that covered a 2 cm by 2 cm area. Different exposure times were realized by changing the speed of the movement and adjusting the distance between consecutive passes. S. aureus was most responsive to the exposure with a reduction in the number of colony forming units of 5.5 log steps in 40 s. All other microorganisms show a more gradual inactivation with exposure times. For all bacteria, a clearing of the treated area is achieved in about 2.5–3.5 min, corresponding to log-reduction factors of 5.5–6.5. Complete inactivation of the yeast requires about 7 min. Both S. aureus and C. kefyr show considerable inactivation also outside the immediate treatment area, while P. aeruginosa and A. baumannii do not. We conclude that differences in the morphologies of the membrane structures are responsible for the diverging results, together with a targeted response to different agents provided with the plasma jet. For the gram negative bacteria, we hold short-lived agents, acting across a short range, responsible, while for the other microorganisms, longer lived species seem more important. Our measurements show that neither heat, ultraviolet radiation, nor the generation of ozone can be responsible for the observed results. The most prominent long lived reaction product found is nitric oxide, which, by itself or through induced chemical reactions, might affect cell viability. [ABSTRACT FROM PUBLISHER]

The design and the electric and emission characteristics of a handheld air plasma spray are presented. The plasma is generated by 60-Hz periodic discharges between two concentrically cylindrical electrodes. A ring magnet is used to rotate arc discharges, which sprays outward by an airflow. The rotation of arc discharges keeps the generated plasma in nonequilibrium state and at relatively low temperature (\sim \!\!55\ ^\circ\C). The plasma effluent still contains high-energy electrons which dissociate molecular oxygen into atomic oxygen. The emission spectroscopy of the plasma plume reveals that the plasma effluent, which carries abundant atomic oxygen, extends from the cap of the plasma spray about 25 mm. Using pigs as the animal model, in vivo tests of stopping wound bleeding and postoperative observation of wound healing by this air plasma spray were performed. The results show that the bleeding from a cut to an ear artery is stopped swiftly; this air plasma spray also shortens wound healing time to about half (from 14 days to 8 days) after stopping the bleeding of a cross-cut wound in the ham area. [ABSTRACT FROM AUTHOR]

Plasma medicine is emerging worldwide, and some promising applications seem to be near the horizon. Direct therapeutic plasma application as the central field of plasma medicine will bring physical plasmas directly on or in a human (or animal) body. Campus PlasmaMed is a research association supported by the German Federal Ministry of Education and Research (BMBF), concentrated in the northeast of Germany and founded to explore promising and safe applications of atmospheric-pressure plasmas in medical therapy based on systematic and interdisciplinary basic research on the interactions of plasma components with living systems. Whereas a broad spectrum of plasma sources dedicated for biomedical applications has been reported during recent years, mainly two basic principles of plasma sources are used in the Campus PlasmaMed: atmospheric-pressure plasma jets and dielectric barrier discharges. A comprehensive assessment of potential risk factors, such as gas temperature, power transfer from plasma to the target, (V)UV radiation emission, or the generation of toxic gases and its release into the adjacencies, which could be dangerous for patients and therapists, has to be done as a basic precondition before any biomedical experiments can be started or a potential therapeutic application can be taken into consideration. Despite the fact that the initial plasma-source characterization and optimization are in the main responsibility of plasma physicists and engineers, potential users from the biomedical field should be integrated as soon as possible to include special needs and constraints for specific applications during early steps of development. This multidisciplinary research cooperation among plasma scientists and engineers on the one side and life scientists and clinicians on the other is one of the main characteristics of the Campus PlasmaMed. Such interdisciplinary cooperation is more than ever required for the characterization of biological effects of plasma sources, which has to be realized by a multistep program, starting with the investigations of plasma–liquid interactions and including a broad spectrum of in vitro tests with cells, as well as cell and tissue cultures up to isolated tissues or organs to be proved finally with animal experiments and clinical trials. Because there are no standardized criteria so far according to which atmospheric-pressure plasma sources can be assessed as to their suitability for medical applications, interdisciplinary results from plasma medical research have to be transferred into rules and standards to guarantee successful and safe practical application, including economic exploitation of plasma-medical research results. [ABSTRACT FROM AUTHOR]

A portable low temperature air plasma torch was used to control bleeding from wounds. As animal models, two pigs were used in the tests: one for the plasma treatment, and the other as the untreated control. Plasma effects on the bleeding times of three types of wounds (straight cut and cross cut in the ham area, and a hole in the saphenous vein of an ear) were examined. The results were that this plasma torch shortened the bleeding time for these three types of wounds from about 3 min to 18 s, about 4 min to 13 s, and 88 s to 15 s, respectively. Emission spectroscopy of the torch was performed to explore the reactive species carried by the plasma effluent of the torch. The results show that this torch carries abundant reactive atomic oxygen (RAO), which is the dominant reactive species in the plasma effluent. RAO can activate erythrocyte–platelet interactions to enhance blood coagulation for plug formation. The present tests indicate that RAO can also penetrate through the skin surrounding the wound to block capillary blood flow to the wound. [ABSTRACT FROM PUBLISHER]

Cold plasma treatment of wounds is gaining much interest, because it will offer a noncontact, painless, and harmless therapy to manage large-area lesions (burn wounds and chronic ulcerations). One of the important issues in plasma wound healing is the safety of the method. In this paper, we study in vitro the effects of plasma treatment on cell death, proliferation, and wound healing. We performed a parametric study of plasma-treated 3T3 fibroblast cells. For the treatment, a cold atmospheric plasma needle (13.56-MHz microjet in helium) was used. Cells were cultured in six well plates and subsequently deposited on the bottom of the well. As a wound model, a scratch was made in the cell culture. Then, the proliferation of the cells from the sidewalls into the scratch was observed by microscopy. It appeared that plasma treatment stimulates the proliferation of cells into the scratch. This suggests that plasma treatment could result in accelerated wound healing. [ABSTRACT FROM AUTHOR]

It is now well known that low-temperature plasmas can inactivate bacteria effectively. At low doses, these plasmas can also help in the proliferation of healthy fibroblasts and detach damaged cells without causing necrosis. The combination of these characteristics leads to the possibility of using plasmas in biomedical applications such as wound healing. Although only limited understanding is available as to the mechanisms whereby plasmas interact with cells (prokaryotic or eukaryotic), it is now well established that the effects of plasmas on biological cells depend on the cell type, the cell concentration, and the medium supporting them. In this paper, we present clear visual evidence of these dependencies in the case of bacteria. Through simple imaging, we show that the size and shape of the inactivation zone depend on the type of bacteria, their initial concentrations, and the medium supporting the cells. [ABSTRACT FROM AUTHOR]

The intersection of plasma filaments in a dielectric barrier discharge with a small wound in the human skin in the context of plasma medicine is investigated with results from a computer model. The relative location of the filament with respect to the wound determines the symmetry of treatment. [ABSTRACT FROM AUTHOR]