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Background: Outbreaks of airborne viral infections, such as COVID-19, can cause panic regarding other severe respiratory syndrome diseases that may develop and affect public health. It is therefore necessary to develop control methods that offer protection against such viruses. Aim of Review: To identify a feasible solution for virus deactivation, we critically reviewed methods of generating reactive oxygen species (ROS), which can attack a wide range of molecular targets to induce antiviral activity, accounting for their flexibility in facilitating host defense mechanisms against a comprehensive range of pathogens. Recently, the role of ROS in microbial decontamination has been critically investigated as a major topic in infectious diseases. ROS can eradicate pathogens directly by inducing oxidative stress or indirectly by promoting pathogen removal through numerous non-oxidative mechanisms, including autophagy, T-cell responses, and pattern recognition receptor signaling. Key scientific concepts of review: In this article, we reviewed possible methods for the in vitro generation of ROS with antiviral activity. Furthermore, we discuss, in detail, the novel and environmentally friendly cold plasma delivery system in the destruction of viruses. This review highlights the potential of ROS as therapeutic mediators to modernize current techniques and improvement on the efficiency of inactivating SARS-CoV2 and other viruses.

The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such coronaviruses.

Abstract Microwave (MW) radiation is increasingly being used for several biological applications. Many investigations have focused on understanding the potential influences of pulsed MW irradiation on biological solutions. The current study aimed to investigate the effects of 3.5 GHz pulsed MW radiation-irradiated liquid solutions on the survival of human cancer and normal cells. Different physiological solutions such as phosphate buffer saline, deionized water, and Dulbecco’s modified Eagle medium (DMEM) for cell culture growth were irradiated with pulsed MW radiation (45 shots with the energy of 1 mJ/shot). We then evaluated physiological effects such as cell viability, metabolic activity, mitochondrial membrane potential, cell cycle, and cell death in cells treated with MW-irradiated biological solutions. As MW irradiation with power density ~ 12 kW/cm2 mainly induces reactive nitrogen oxygen species in deionized water, it altered the cell cycle, membrane potential, and cell death rates in U373MG cells due to its high electric field ~ 11 kV/cm in water. Interestingly, MW-irradiated cell culture medium and phosphate-buffered saline did not alter the cellular viability and metabolic energy of cancer and normal cells without affecting the expression of genes responsible for cell death. Taken together, MW-irradiated water can alter cellular physiology noticeably, whereas irradiated media and buffered saline solutions induce negligible or irrelevant changes that do not affect cellular health.

Over the past few decades, microwave (MW) radiation has been widely used, and its biological effects have been extensively investigated. However, the effect of MW radiation on human skin biology is not well understood. We study the effects of pulsed high-power microwaves (HPMs) on melanoma (G361 and SK-Mel-31) and normal human dermal fibroblast (NHDF) cells. A pulsed power generator (Chundoong) was used to generate pulsed HPMs (dominant frequency: 3.5 GHz). For treatment 1, 5, 15, and 45 shots are given to cells in which the electromagnetic energy of 0.6 J was delivered to the cells at each trigger shot. Cell viability, proliferation rate, apoptosis, cell death, metabolic activity, and oxygen-free radical regulation were evaluated after the MW exposure at low and high doses. MW exposure increased the viabilities and proliferation rates of both melanoma cell lines in a dose-dependent manner, while no significant effects on the fibroblast cells were observed. We found an elevated level of ATP and mitochondrial activity in melanoma cells. Also, it was observed that MW exposure did not affect cell death in melanoma and fibroblast cells. A polymerase chain reaction analysis indicated that the MWs induced dose-dependent proliferation markers without affecting the cell cycle and apoptotic genes in the melanoma cells. Our findings show the differential effects of the MW radiation on the melanoma cells, compared to those on the fibroblast cells. Keywords: Electromagnetic energy, Melanoma cell, Fibroblast skin cell, Proliferation, Adenosine triphosphate, Mitochondrial activity

Excess amounts of redox stress and failure to regulate homeostatic levels of reactive species are associated with several skin pathophysiologic conditions. Nonmalignant cells are assumed to cope better with higher reactive oxygen and nitrogen species (RONS) levels. However, the effect of periodic stress on this balance has not been investigated in fibroblasts in the field of plasma medicine. In this study, we aimed to investigate intrinsic changes with respect to cellular proliferation, cell cycle, and ability to neutralize the redox stress inside fibroblast cells following periodic redox stress in vitro. Soft jet plasma with air as feeding gas was used to generate plasma-activated medium (PAM) for inducing redox stress conditions. We assessed cellular viability, energetics, and cell cycle machinery under oxidative stress conditions at weeks 3, 6, 9, and 12. Fibroblasts retained their usual physiological properties until 6 weeks. Fibroblasts failed to overcome the redox stress induced by periodic PAM exposure after 6 weeks, indicating its threshold potential. Periodic stress above the threshold level led to alterations in fibroblast cellular processes. These include consistent increases in apoptosis, while RONS accumulation and cell cycle arrest were observed at the final stages. Currently, the use of NTP in clinical settings is limited due to a lack of knowledge about fibroblasts’ behavior in wound healing, scar formation, and other fibrotic disorders. Understanding fibroblasts’ physiology could help to utilize nonthermal plasma in redox-related skin diseases. Furthermore, these results provide new information about the threshold capacity of fibroblasts and an insight into the adaptation mechanism against periodic oxidative stress conditions in fibroblasts.

Although the skin is constantly subjected to endogenous and exogenous stress, it maintains a homeostatic state through wound repair and regeneration pathways. Treatment for skin diseases and injury requires a significant understanding of the various mechanisms and interactions that occur within skin cells. Keratinocytes and fibroblasts interact with each other and act as key players in the repair process. Although fibroblasts and keratinocytes are widely studied in wound healing and skin remodeling under different conditions, the influence of redox stress on keratinocyte-fibroblast crosstalk has not been thoroughly investigated. In this study, we used cold atmospheric plasma (CAP) to generate and deliver oxidative stress to keratinocytes and fibroblasts and to assess its impact on their interactions. To this end, we used a well-established in vitro 3D co-culture model imitating a realistic scenario. Our study shows that low CAP exposure is biocompatible and does not affect the viability or energetics of fibroblasts and keratinocytes. Exposure to low doses of CAP enhanced the proliferation rate of cells and stimulated the expression of key genes (KGF, MMP2, GMCSF, IL-6, and IL-8) in fibroblasts, indicating the activation and initiation of the skin repair process. Additionally, enhanced migration was observed under co-culture conditions under the given redox stress conditions, and expression of the upstream regulator and the effectors of the Hippo pathway (YAP and CYR61, respectively), which are associated with enhanced migration, were elevated. Overall, this study reinforces the application of CAP and redox stress in skin repair physiology.

Natural products with medicinal properties are among alternative therapies of interest due to their high body tolerance. We aimed to determine whether nonthermal gas plasma could enhance the medicinal value of Flammulina velutipes mushrooms. Generated gas plasma was characterized by its emission spectrum in ambient air, pH, temperature, and H2O2 and NOx concentrations after exposure for various periods. Phenolic and flavonoid contents in the extracts were measured using antioxidant assays and Fourier transform infrared and ultraviolet-visible spectroscopy. We analyzed the effects of the plasma-treated mushroom-derived extracts against breast carcinoma using the MCF7 and MDA-MB231 cell lines. The extracts significantly and concentration dependently inhibited the growth of breast cancer cells without inducing toxicity in normal MCF10A cells, and induced apoptosis via oxidative stress, evidenced by DNA damage (γ-H2AX foci formation), and increased the population of MCF7 breast cancer cells arrested in the G2/M phase of the cell cycle. The extracts also induced mitochondrion-mediated apoptosis of MCF7 cells through cytochrome c release and caspase cleavage activity. The plasma improved the biological activity of mushrooms by increasing their phenolic compounds that prevented the growth of breast cancer cells in vitro.

In recent decades, the use of plants as a natural remedy has been widely applied in traditional medicine and the treatment of various diseases, including cancer. However, in order to confirm the potential benefits of anticancer drug development from natural sources, in-depth screening assessments are necessary. In the present study, we aimed to evaluate the cytotoxic effects of eight medicinal plants against breast carcinoma and hepatocellular carcinoma cell lines. Remarkably, among all the tested plant extracts, Pyracantha angustifolia and Paullinia cupana extracts showed maximum inhibition in the two cancer cell line models, as detected by cell viability assays, but not in normal mammary epithelial cells. Moreover, induction of cell cycle arrest was seen in both cancer cell models after treatment with extracts derived from the fruits of P. angustifolia and the seeds of P. cupana. Phytochemical and antioxidant analyses demonstrated the presence of high phenolic and flavonoid contents, including an increase in 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity. The growth inhibition of human breast carcinoma and hepatocellular carcinoma cells mediated by both extracts appears to be associated with apoptosis and upregulated expression of pro-apoptotic genes (caspase-3, caspase-7, tumor suppressor protein-p53, cytochrome c, poly (ADP-ribose) polymerase, p53 upregulated modulator of apoptosis, and Bcl-2-associated X-protein). Together, these results indicate that P. angustifolia and P. cupana offer a promising approach for the development of anticancer agents. However, further detailed research is required to make these plants applicable for therapeutic use.

Implantation of the blastocyst stage embryo into the maternal endometrium is a critical determinant and a rate-limiting process for successful pregnancy. Embryo implantation requires synchronized changes in the endometrium before and after arrival of blastocyst into the uterine cavity. Extensive cross talks occur between the fetal and maternal compartments around the time of implantation which are reflected by morphologic, biochemical and molecular changes in the endometrial cells and the differentiating trophoblast cells. The embryo induced morphologic changes include occurrence of epithelial plaque reaction, stromal compaction and decidualization. Embryonic signals also alter the expression of a large number of transcription factors, growth factors and their receptors and integrins. Thus the embryo superimposes a unique signature on the receptive endometrium for successful implantation. Functionally, the embryo-endometrial cross talk is essential for endowing a “selector activity” to the receptive endometrium to ensure implantation of only a developmentally competent embryo. On selection, the decidua creates a conducive microenvironment for trophoblast invasion leading to placentation. Clinical evidences suggest that along with receptivity, a defective “selector” activity of the receptive uterus may be a cause of infertility and recurrent miscarriages. Defects in trophoblast invasion are associated with pregnancy complications like preeclampsia and intra-uterine growth retardation. It is envisaged that understanding of the embryo-endometrial dialogue leading to the “selector” activity, aids in development of appropriate therapeutic modalities for infertility related disorders and miscarriages. Conversely, it might also benefit the development of anti-implantation drugs for contraception.