Cold atmospheric plasma (CAP): a revolutionary approach in dermatology and skincare.

Cold atmospheric plasma (CAP) technology has emerged as a revolutionary therapeutic technology in dermatology, recognized for its safety, effectiveness, and minimal side effects. CAP demonstrates substantial antimicrobial properties against bacteria, viruses, and fungi, promotes tissue proliferation and wound healing, and inhibits the growth and migration of tumor cells. This paper explores the versatile applications of CAP in dermatology, skin health, and skincare. It provides an in-depth analysis of plasma technology, medical plasma applications, and CAP. The review covers the classification of CAP, its direct and indirect applications, and the penetration and mechanisms of action of its active components in the skin. Briefly introduce CAP's suppressive effects on microbial infections, detailing its impact on infectious skin diseases and its specific effects on bacteria, fungi, viruses, and parasites. It also highlights CAP's role in promoting tissue proliferation and wound healing and its effectiveness in treating inflammatory skin diseases such as psoriasis, atopic dermatitis, and vitiligo. Additionally, the review examines CAP's potential in suppressing tumor cell proliferation and migration and its applications in cosmetic and skincare treatments. The therapeutic potential of CAP in treating immune-mediated skin diseases is also discussed. CAP presents significant promise as a dermatological treatment, offering a safe and effective approach for various skin conditions. Its ability to operate at room temperature and its broad spectrum of applications make it a valuable tool in dermatology. Finally, introduce further research is required to fully elucidate its mechanisms, optimize its use, and expand its clinical applications.

Epilipidomics reveals lipid fatty acid and headgroup modification in gas plasma-oxidized biomembranes.

Lipids, possessing unsaturated fatty acid chains and polar regions with nucleophilic heteroatoms, represent suitable oxidation targets for autologous and heterologous reactive species. Lipid peroxidation products (LPPs) are highly heterogeneous, including hydroperoxides, alkenals, chlorination, or glycation. Accordingly, delineation of lipid targets, species type, resulting products, and oxidation level remains challenging. To this end, liposomal biomimetic models incorporating a phosphatidylcholine, -ethanolamine, and a sphingomyelin were used to deconvolute effects on a single lipid scale to predict potential modification product outcomes. To introduce oxidative modifications, gas plasma technology, a powerful pro-oxidant tool to promote LPP formation by forming highly abundant reactive species in the gas and liquid phases, was employed to liposomes. The plasma parameters (gas type/combination) were modified to modulate the resulting species-profile and LPP formation by enriching specific reactive species types over others. HR-LC-MS (Münzel and et al., 2017) [2] was employed for LPP identification. Moreover, the heavy oxygen isotope 18O was used to trace O2-incorporation into LPPs, providing first information on the plasma-mediated lipid peroxidation mechanism. We found that combination of lipid class and gas composition predetermined the type of attack: admixture of O2 to the plasma and the presence of nitrogen atoms with free electrons in the molecule lead to chlorination of the amide bond and headgroup. Here, atomic oxygen driven formation of hypochlorite is the major reactive species. In contrast, POPC yields mainly to LPPs with oxidation of the oleic acid tail, especially truncations, epoxidation, and hydroperoxide formation. Here, singlet oxygen is assumingly the major driver. 18O labelling revealed that gas phase derived reactive species are dominantly incorporated into the LPPs, supporting previous findings on gas-liquid interface chemistry. In summary, we here provided the first insights into gas plasma-mediated lipid peroxidation, which, employed in more complex cell and tissue models, may support identifying mechanisms of actions in plasma medicine.

Cold atmospheric plasma activated media selectively affects human head and neck cancer cell lines.

OBJECTIVE: Cold atmospheric plasma (CAP) is a novel approach for cancer treatment. It can be used to treat liquids-plasma-activated media (PAM)-which are then transferred to the target as an exogenous source of reactive oxygen and nitrogen species (RONS). The present study aimed at chemically characterizing different PAM and assessing their in vitro selectivity against head and neck cancer cells (HNC). METHODS: PAM were obtained by exposing 2 and 5 mL of cell culture medium to CAP for 5, 10 and 20 min at a 6 mm working distance. Anions kinetics was evaluated by ion chromatography. Cell proliferation inhibition, apoptosis occurrence, and cell cycle modifications were assessed by MTS and flow cytometry, on human epidermal keratinocyte (HaCaT) and HNC cell lines HSC3, HSC4 and A253. RESULTS: The 2 mL conditions showed a significant reduction in cell proliferation whereas for the 5 mL the effect was milder, but the time-dependence was more evident. HaCaT were unaffected by the 5 mL PAM, indicating a selectivity for cancer cells. CONCLUSIONS: The media chemical composition modified by CAP exposure influenced cell proliferation by modulating cell cycle and inducing apoptosis in cancer cells, without affecting normal cells.

Determination of the combined effect of grape seed extract and cold atmospheric plasma on foodborne pathogens and their environmental stress knockout mutants.

The study aimed to explore the antimicrobial efficacy of grape seed extract (GSE) and cold atmospheric plasma (CAP) individually or in combination against L. monocytogenes and E. coli wild type (WT) and their isogenic mutants in environmental stress genes. More specifically, we examined the effects of 1% (wt/vol) GSE, 4 min of CAP treatment, and their combined effect on L. monocytogenes 10403S WT and its isogenic mutants ΔsigB, ΔgadD1, ΔgadD2, ΔgadD3, as well as E. coli K12 and its isogenic mutants ΔrpoS, ΔoxyR, and ΔdnaK. In addition, the sequence of the combined treatments was tested. A synergistic effect was achieved for all L. monocytogenes strains when exposure to GSE was followed by CAP treatment. However, the same effect was observed against E. coli strains, only for the reversed treatment sequence. Additionally, L. monocytogenes ΔsigB was more sensitive to the individual GSE and the combined GSE/CAP treatment, whereas ΔgadD2 was more sensitive to CAP, as compared to the rest of the mutants under study. Individual GSE exposure was unable to inhibit E. coli strains, and individual CAP treatment resulted in higher inactivation of E. coli in comparison to L. monocytogenes with the strain ΔrpoS appearing the most sensitive among all studied strains. Our findings provide a step toward a better understanding of the mechanisms playing a role in the tolerance/sensitivity of our model Gram-positive and Gram-negative bacteria toward GSE, CAP, and their combination. Therefore, our results contribute to the development of more effective and targeted antimicrobial strategies for sustainable decontamination.IMPORTANCEAlternative approaches to conventional sterilization are gaining interest from the food industry, driven by (i) the consumer demand for minimally processed products and (ii) the need for sustainable, environmentally friendly processing interventions. However, as such alternative approaches are milder than conventional heat sterilization, bacterial pathogens might not be entirely killed by them, which means that they could survive and grow, causing food contamination and health hazards. In this manuscript, we performed a systematic study of the impact of antimicrobials derived from fruit industry waste (grape seed extract) and cold atmospheric plasma on the inactivation/killing as well as the damage of bacterial pathogens and their genetically modified counterparts, for genes linked to the response to environmental stress. Our work provides insights into genes that could be responsible for the bacterial capability to resist/survive those novel treatments, therefore, contributing to the development of more effective and targeted antimicrobial strategies for sustainable decontamination.

Plasma Control: A Review of Developments and Applications of Plasma Medicine Control Mechanisms.

Cold atmospheric plasmas (CAPs) within recent years have shown great promise in the field of plasma medicine, encompassing a variety of treatments from wound healing to the treatment of cancerous tumors. For each subsequent treatment, a different application of CAPs has been postulated and attempted to best treat the target for the most effective results. These treatments have varied through the implementation of control parameters such as applied settings, electrode geometries, gas flow, and the duration of the treatment. However, with such an extensive number of variables to consider, scientists and engineers have sought a means to accurately control CAPs for the best-desired effects in medical applications. This paper seeks to investigate and characterize the historical precedent for the use of plasma control mechanisms within the field of plasma medicine. Current control strategies, plasma parameters, and control schemes will be extrapolated through recent developments and successes to gain better insight into the future of the field and the challenges that are still present in the overall implementation of such devices. Proposed approaches, such as data-driven machine learning, and the use of closed-loop feedback controls, will be showcased as the next steps toward application.

Cold Atmospheric Plasma Induces Growth Arrest and Apoptosis in Neurofibromatosis Type 1-Associated Peripheral Nerve Sheath Tumor Cells.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder resulting from mutations in the NF1 gene. Patients harboring these mutations are predisposed to a spectrum of peripheral nerve sheath tumors (PNSTs) originating from Schwann cells, of which malignant peripheral nerve sheath tumors (MPNSTs) are the deadliest, with limited treatment options. Therefore, an unmet need still exists for more effective therapies directed at these aggressive malignancies. Cold atmospheric plasma (CAP) is a reactive oxygen species (ROS) and reactive nitrogen species (RNS) generating ionized gas that has been proposed to be a potential therapeutic modality for cancer. In this study, we sought to determine the effects of CAP on NF1-associated PNSTs. Utilizing established mouse and human cell lines to interrogate the effects of CAP in both in vitro and in vivo settings, we found that NF1-associated PNSTs were highly sensitive to CAP exposure, resulting in cell death. To our knowledge, this is the first application of CAP to NF1-associated PNSTs and provides a unique opportunity to study the complex biology of NF1-associated tumors.

Cold atmospheric plasma therapy as a novel treatment for Berlin Heart EXCOR pediatric cannula infections.

BACKGROUND: Cold atmospheric plasma (CAP) therapy has been recognized as effective treatment option for reducing bacterial load in chronic wounds, such as adult ventricular assist device (VAD) driveline exit-site infections. Currently, there have been no reports on the safety and efficacy of CAP therapy for pediatric cannula infections and inflammations in paracorporeal pulsatile VADs. METHODS: The mechanical strength of Berlin Heart EXCOR cannulas were tested both before and after CAP treatment (SteriPlas, Adtec Healthcare Limited, UK) to prove material safety. A ring tensile test of 20 untreated and 20 CAP-treated (5 min) EXCOR cannulas (Ø12mm), assessed the force at the breaking point of the cannulas (Fmax), at 25% (F25%) and 50% (F50%) of the maximum displacement. Additionally, the scanning electron microscope (SEM) micrographs for both groups examined any surface changes. Finally, the case of a 13-year-old male EXCOR patient with cannula infections, treated with CAP over 100 days, is presented. RESULTS: The in vitro measurements revealed no statistically significant differences in mechanical strength between the control and CAP group for F25% (8.18 ± 0.36 N, vs. 8.02 ± 0.43 N, p = 0.21), F50% (16.87 ± 1.07 N vs. 16.38 ± 1.32 N, p = 0.21), and FMAX (44.55 ± 3.24 N vs. 42.83 ± 4.32 N, p = 0.16). No surface structure alterations were identified in the SEM micrographs. The patient's cannula exit-sites showed a visible improvement in DESTINE wound staging, reduction in bacterial load and inflammatory parameters after CAP treatment without any side effects. CONCLUSION: Overall, CAP therapy proved to be a safe and effective for treating EXCOR cannula exit-site wound healing disorders in one pediatric patient, but further studies should investigate this therapy in more detail.

Enhanced Corrosion Protection of Printed Circuit Board Electronics using Cold Atmospheric Plasma-Assisted SiOx Coatings.

The miniaturization and widespread deployment of electronic devices across diverse environments have heightened their vulnerability to corrosion, particularly affecting copper traces within printed circuit boards (PCBs). Conventional protective methods, such as conformal coatings, face challenges including the necessity for a critical thickness to ensure effective barrier properties and the requirement for multiple steps of drying and curing to eliminate solvent entrapment within polymer coatings. This study investigates cold atmospheric plasma (CAP) as an innovative technique for directly depositing ultrathin silicon oxide (SiOx) coatings onto copper surfaces to enhance corrosion protection in PCBs. A systematic investigation was undertaken to examine how the scanning speed of the CAP deposition head impacts the film quality and corrosion resistance. The research aims to determine the optimal scanning speed of the CAP deposition head that achieves complete surface coverage while promoting effective cross-linking and minimizing unreacted precursor entrapment, resulting in superior electrical barrier and mechanical properties. The CAP coating process demonstrated the capability of depositing SiOx onto copper surfaces at various thicknesses ranging from 70 to 1110 nm through a single deposition process by simply adjusting the scanning speed of the plasma head (5-75 mm/s). Evaluation of material corrosion barrier characteristics revealed that scanning speeds of 45 mm/s of the plasma deposition head provided an effective coating thickness of 140 nm, exhibiting superior corrosion resistance (30-fold) compared to that of uncoated copper. As a proof of concept, the efficacy of CAP-deposited SiOx coatings was demonstrated by protecting an LED circuit in saltwater and by coating printed circuits for potential agricultural sensor applications. These CAP-deposited coatings offer performance comparable to or superior to traditional conformal polymeric coatings. This research presents CAP-deposited SiOx coatings as a promising approach for effective and scalable corrosion protection in miniaturized electronics.

Impact of Cold Atmospheric Plasma Pretreatment on the Recovery of Phenolic Antioxidants from Spent Coffee Grounds.

In the present study, cold atmospheric plasma (CAP) was employed as a pretreatment method for the extraction of phenolic compounds from spent coffee grounds (SCGs). The impact of CAP treatment conditions, i.e., thickness of the SCGs layer (mm), distance between the plasma source and the SCGs layer (mm) and duration of CAP treatment (min), on the total phenol content, in vitro antioxidant activity, as well as caffeine and chlorogenic acid content of SCGs, was investigated. The process parameters were optimized with the aid of response surface methodology (RSM). After optimizing the CAP pretreatment conditions, the CAP-treated SCGs were subjected to ultrasound-assisted extraction using ethanol as the extraction solvent. The optimum conditions for CAP treatment identified, i.e., thickness, 1 mm; distance, 16 mm; and duration, 15 min, led to a significant enhancement in the recovery of bioactive compounds from SCGs compared to those obtained from untreated SCGs. Total phenolic content and antioxidant activity significantly increased (i.e., TPC from 19.0 ± 0.7 to 24.9 ± 1.4 mg GAE/100 g dry SCGs, ADPPH from 106.7 ± 5.01 to 112.3 ± 4.3 µmol Trolox/100 g dry SCGs, AABTS from 106.7 ± 5.01 to 197.6 ± 5.8 µmol Trolox/100 g dry SCGs, ACUPRAC from 17938 ± 157 to 18299 ± 615 µmol Trolox/100 g dry SCGs). A significant increase in caffeine content from 799.1 ± 65.1 mg to 1064 ± 25 mg/100 g dry SCGs and chlorogenic acid content from 79.7 ± 15.3 mg to 111.3 ± 3.3 mg/100 g dry SCGs, was also observed. Overall, CAP pre-treatment can be used to enhance the recovery of bioactive compounds from SCGs.

Realtime RONS monitoring of cold plasma-activated aqueous media based on time-resolved phosphorescence spectroscopy.

Besides many efforts on the detection and quantification of reactive oxygen and nitrogen species (RONSs) in the aqueous media activated by the cold atmospheric plasma, to get a better insight into the dominant mechanism and reactive species in medical applications, a challenge still remains in monitoring the real-time evaluation of them. To this end, in the present work, relying on the photonic technology based on the time-resolved phosphorescence spectroscopy, real-time tracking of RONSs concentration in treated aqueous media is achieved by following the dissolved oxygen (DO) production/consumption. Using a photonic-based dissolved oxygen sensor, the dependence of real-time RONS concentration evaluation of plasma activated medium on plasma nozzle distance, non-thermal plasma jet exposure time, various culture media, and presence of cells is investigated. Analyzing the results, the activation parameters including the time of reaching maximum RONS concentration after treatment and defined activation parameter [Formula: see text] of the treated media for each case is measured and compared together. Moreover, employing the scavengers related to two involved ROSs, the dominant chemical reactions as well as ROS contributed in the DMEM medium is determined. As a promising result, the obtained correlation between the real-time DO level and viability and toxicity of the cancer cells, MCF-7 breast cancer cells, could enable us to exploit the present photonic setup as an alternative technique for the biological assessment.

In Vitro Safety Study on the Use of Cold Atmospheric Plasma in the Upper Respiratory Tract.

Cold atmospheric plasma (CAP) devices generate reactive oxygen and nitrogen species, have antimicrobial and antiviral properties, but also affect the molecular and cellular mechanisms of eukaryotic cells. The aim of this study is to investigate CAP treatment in the upper respiratory tract (URT) to reduce the incidence of ventilator-associated bacterial pneumonia (especially superinfections with multi-resistant pathogens) or viral infections (e.g., COVID-19). For this purpose, the surface-microdischarge-based plasma intensive care (PIC) device was developed by terraplasma medical GmbH. This study analyzes the safety aspects using in vitro assays and molecular characterization of human oral keratinocytes (hOK), human bronchial-tracheal epithelial cells (hBTE), and human lung fibroblasts (hLF). A 5 min CAP treatment with the PIC device at the "throat" and "subglottis" positions in the URT model did not show any significant differences from the untreated control (ctrl.) and the corresponding pressurized air (PA) treatment in terms of cell morphology, viability, apoptosis, DNA damage, and migration. However, pro-inflammatory cytokines (MCP-1, IL-6, and TNFα) were induced in hBTE and hOK cells and profibrotic molecules (collagen-I, FKBP10, and αSMA) in hLF at the mRNA level. The use of CAP in the oropharynx may make an important contribution to the recovery of intensive care patients. The results indicate that a 5 min CAP treatment in the URT with the PIC device does not cause any cell damage. The extent to which immune cell activation is induced and whether it has long-term effects on the organism need to be carefully examined in follow-up studies in vivo.

Proposing an Affordable Plasma Device for Polymer Surface Modification and Microbial Inactivation.

This study proposes an affordable plasma device that utilizes a parallel-plate dielectric barrier discharge geometry with a metallic mesh electrode, featuring a straightforward 3D-printed design. Powered by a high-voltage supply adapted from a cosmetic plasma device, it operates on atmospheric air, eliminating the need for gas flux. Surface modification of polyethylene treated with this device was characterized and showed that the elemental composition after 15 min of plasma treatment decreased the amount of C to ~80 at% due to the insertion of O (~15 at%). Tested against Candida albicans and Staphylococcus aureus, the device achieved a reduction of over 99% in microbial load with exposure times ranging from 1 to 10 min. Simultaneously, the Vero cell viability remained consistently high, namely between 91% and 96% across exposure times. These results highlight this device's potential for the surface modification of materials and various infection-related applications, boasting affordability and facilitating effective antimicrobial interventions.

Guided Plasma Application in Dentistry-An Alternative to Antibiotic Therapy.

Cold atmospheric plasma (CAP) is a promising alternative to antibiotics and chemical substances in dentistry that can reduce the risk of unwanted side effects and bacterial resistance. AmbiJet is a device that can ignite and deliver plasma directly to the site of action for maximum effectiveness. The aim of the study was to investigate its antimicrobial efficacy and the possible development of bacterial resistance. The antimicrobial effect of the plasma was tested under aerobic and anaerobic conditions on bacteria (five aerobic, three anaerobic (Gram +/-)) that are relevant in dentistry. The application times varied from 1 to 7 min. Possible bacterial resistance was evaluated by repeated plasma applications (10 times in 50 days). A possible increase in temperature was measured. Plasma effectively killed 106 seeded aerobic and anaerobic bacteria after an application time of 1 min per 10 mm2. Neither the development of resistance nor an increase in temperature above 40 °C was observed, so patient discomfort can be ruled out. The plasma treatment proved to be effective under anaerobic conditions, so the influence of ROS can be questioned. Our results show that AmbiJet efficiently eliminates pathogenic oral bacteria. Therefore, it can be advocated for clinical therapeutic use.

Multiple RONS-Loaded Plasma-Activated Ice Microneedle Patches for Transdermal Treatment of Psoriasis.

Cold atmospheric plasma (CAP) is a fledgling therapeutic technique for psoriasis treatment with noninvasiveness, but clinical adoption has been stifled by the insufficient production and delivery of plasma-generated reactive oxygen and nitrogen species (RONS). Herein, patches of air-discharge plasma-activated ice microneedles (PA-IMNs) loaded with multiple RONS are designed for local transdermal delivery to treat psoriasis as an alternative to direct CAP irradiation treatment. By mixing two RONS generated by the air-discharge plasma in the NOx mode and O3 mode, abundant high-valence RONS are produced and incorporated into PA-IMNs via complex gas-gas and gas-liquid reactions. The PA-IMNs abrogate keratinocyte overproliferation by inducing reactive oxygen species (ROS)-mediated loss of the mitochondrial membrane potential and apoptosis of keratinocytes. The in vivo transdermal treatment confirms that PA-IMNs produce significant anti-inflammatory and therapeutic actions for imiquimod (IMQ)-induced psoriasis-like dermatitis in mice by inhibiting the release of associated inflammatory factors while showing no evident systemic toxicity. Therefore, PA-IMNs have a large potential in transdermal delivery platforms as they overcome the limitations of using CAP directly in the clinical treatment of psoriasis.

Therapeutic efficacy of cold atmospheric plasma in four golden retrievers with acute otitis externa.

BACKGROUND: Cold atmospheric plasma (CAP) is a new therapeutic tool used to treat various skin diseases in humans and animals. OBJECTIVE: To evaluate the effect of CAP in the treatment of canine acute otitis externa (AOE). ANIMALS: Four client-owned golden retriever dogs with bilateral AOE. METHODS AND MATERIALS: After cleaning with a commercial ear cleanser, right ears (STANDARD group) were treated with an antibiotic/antifungal/corticosteroid combination and left ears (CAP group) were treated with CAP every three days for a total of four treatments. Cytological score and otitis index score (OTIS)3 were recorded for each ear on Day (D)0, D10 and D15. At D10 and D15, owners and investigators recorded an overall assessment. RESULTS: In both groups, OTIS3 and cytological score decreased over the study period. The overall assessment scale ranged from moderate to excellent in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: Cold atmospheric plasma treatment showed equal therapeutic effect compared with a commercial topical anti-inflammatory and antimicrobial ear treatment.

Enhanced neural recovery and reduction of secondary damage in spinal cord injury through modulation of oxidative stress and neural response.

Spinal cord injury (SCI) presents a critical medical challenge, marked by substantial neural damage and persistent functional deficits. This study investigates the therapeutic potential of cold atmospheric plasma (CAP) for SCI, utilizing a tailored dielectric barrier discharge (DBD) device to conduct comprehensive in vivo and in vitro analyses. The findings show that CAP treatment significantly improves functional recovery after SCI, reduces neuronal apoptosis, lowers inflammation, and increases axonal regeneration. These findings illustrate the efficacy of CAP in fostering a conducive environment for recovery by modulating inflammatory responses, enhancing neuronal survival, and encouraging regenerative processes. The underlying mechanism involves CAP's reactive oxygen species (ROS) reduction, followed by activating antioxidant enzymes. These findings position CAP as a pioneering approach for spinal cord injury (SCI) treatment, presenting opportunities for improved neural recovery and establishing a new paradigm in SCI therapy.

Healing wounds with plasma-activated hydrogel therapy.

Chronic wound infections are a silent pandemic in danger of becoming a global healthcare crisis. Innovations to control infections and improve healing are required. In the context of this challenge, researchers are exploiting plasma-activated hydrogel therapy (PAHT) for use either alone or in combination with other antimicrobial strategies. PAHT involves the cold atmospheric pressure plasma activation of hydrogels with reactive oxygen and nitrogen species to decontaminate infections and promote healing. This opinion article describes PAHT for wound treatment and provides an overview of current research and outstanding challenges in translating the technology for medical use. A 'blueprint' of an autonomous PAHT is presented in the final section that can move the management and treatment of wounds from the clinical setting to the community.

A Two-Stage Transferred Cold Atmospheric Plasma as a Unique Therapeutic Strategy for Targeting Colon Cancer Stem Cells.

The study examines the induction of apoptosis in colon cancer stem cells (CCSCs) within a 3D culture setting, employing an innovative cold atmospheric plasma (CAP) transmission method known as two-stage transferred cold atmospheric plasma (TS-TCAP). TS-TCAP is a partially or fully ionized non-thermal gaseous mixture that comprises photons, charged and neutral particles, and free radicals, which has gained traction in biomedical applications such as cancer therapy. TS-TCAP impacts CCSCs via a continuous, two-step transport process, facilitating the efficient delivery of reactive oxygen and nitrogen species (RONS). The key cellular factors of CCSCs impacted by TS-TCAP treatment, encompassing the secretion and expression levels of IL-6 and IL-8, apoptotic cell count, and expression of BAX, BCL-2, and KI-67 proteins, were evaluated using qrt-ELISA, Annexin V, and qrt-PCR procedures, respectively. The outcomes of CCSCs treatment with TS-TCAP reveal a notable rise in the number of apoptotic cells (P<0.0001), diminished secretion, and gene expression of IL-6 and IL-8 (P<0.0001), accompanied by favorable alterations in BCL-2 and BAX gene expression (P<0.0001). Additionally, a notable decrease in KI-67 expression was observed, correlating with a reduction in CCSCs proliferation (P<0.0001). As well, this study underscores the anti-cancer potential of TS-TCAP, showcasing its efficacy in reducing CCSCs survival rates. However, further pre-clinical and clinical trials are necessary to evaluate CAP's efficacy, safety, and potential synergistic effects with other therapies thoroughly. Overall, TS-TCAP presents a promising alternative for CCSCs treatment, pending further investigation and refinement.

Cold atmospheric plasma inactivates Aspergillus flavus and Fusarium keratoplasticum biofilms and conidia in vitro.

Introduction. Aspergillus flavus and Fusarium keratoplasticum are common causative pathogens of fungal keratitis (FK), a severe corneal disease associated with significant morbidity and vision loss. Escalating incidence of antifungal resistance to available antifungal drugs poses a major challenge to FK treatment. Cold atmospheric plasma (CAP) is a pioneering nonpharmacologic antimicrobial intervention that has demonstrated potential as a broad-spectrum antifungal treatment.Gap statement. Previous research highlights biofilm-associated resistance as a critical barrier to effective FK treatment. Although CAP has shown promise against various fungal infections, its efficacy against biofilm and conidial forms of FK pathogens remains inadequately explored.Aim. This study aims to investigate the antifungal efficacy of CAP against clinical fungal keratitis isolates of A. flavus and F. keratoplasticum in vitro.Methodology. Power parameters (22-27 kVpp, 300-400 Hz and 20-80 mA) of a dielectric barrier discharge CAP device were optimized for inactivation of A. flavus biofilms. Optimal applied voltage and total current were applied to F. keratoplasticum biofilms and conidial suspensions of A. flavus and F. keratoplasticum. The antifungal effect of CAP treatment was investigated by evaluating fungal viability through means of metabolic activity, c.f.u. enumeration (c.f.u. ml-1) and biofilm formation.Results. For both fungal species, CAP exhibited strong time-dependent inactivation, achieving greater than 80 % reduction in metabolic activity and c.f.u. ml-1 within 300 s or less, and complete inhibition after 600 s of treatment.Conclusion. Our findings indicate that CAP is a promising broad-spectrum antifungal intervention. CAP treatment effectively reduces fungal viability in both biofilm and conidial suspension cultures of A. flavus and F. keratoplasticum, suggesting its potential as an alternative treatment strategy for fungal keratitis.

Plasma-generated RONS in liquid transferred into cryo-microneedles patch for skin treatment of melanoma.

Malignant melanoma is the most lethal form of skin cancer. As a promising anti-cancer agent, plasma-activated water (PAW) rich in reactive oxygen and nitrogen species (RONS) has shown significant potential for melanoma treatment. However, rapid decay of RONS and inefficient delivery of PAW in conventional injection methods limit its practical applications. To address this issue, here we report a new approach for the production of plasma-activated cryo-microneedles (PA-CMNs) patches using custom-designed plasma devices and processes. Our innovation is to incorporate PAW into the PA-CMNs that are fabricated using a fast cryogenic micro-molding method. It is demonstrated that PA-CMNs can be easily inserted into skin to release RONS and slow the decay of RONS thereby prolonging their bioactivity and effectiveness. The new insights into the effective melanoma treatment suggest that the rich mixture of RONS within PA-CMNs prepared by custom-developed hybrid plasma-assisted configuration induces both ferroptosis and apoptosis to selectively kill tumor cells. A significant inhibition of subcutaneous A375 melanoma growth was observed in PA-CMNs-treated tumor-bearing nude mice without any signs of systemic toxicity. The new approach based on PA-CMNs may potentially open new avenues for a broader range of disease treatments.