Applications of cold atmospheric plasma in immune-mediated inflammatory diseases via redox homeostasis: evidence and prospects.

As a representative technology in plasma medicine, cold atmospheric plasma (CAP) has beneficial outcomes in surface disinfection, wound repair, tissue regeneration, solid tumor therapy. Impact on immune response and inflammatory conditions was also observed in the process of CAP treatment. Relevant literatures were collected to assess efficacy and summarize possible mechanisms of the innovation. CAP mediates alteration in local immune microenvironment mainly through two ways. One is to down-regulate the expression level of several cytokines, impeding further conduction of immune or inflammatory signals. Intervening the functional phenotype of cells through different degree of oxidative stress is the other approach to manage the immune-mediated inflammatory disorders. A series of preclinical and clinical studies confirmed the therapeutic effect and side effects free of CAP. Moreover, several suggestions proposed in this manuscript might help to find directions for future investigation.

Plasma-Activated Solutions Mitigates DSS-Induced Colitis via Restoring Redox Homeostasis and Reversing Microbiota Dysbiosis.

Ulcerative colitis is a chronic disease that increases the risk of developing colorectal cancer. Conventional medications are limited by drug delivery and a weak capacity to modulate the inflammatory microenvironment. Further, gut microbiota dysbiosis caused by mucosal damage and dysregulated redox homeostasis leads to frequent recurrence. Therefore, promoting mucosal healing and restoring redox homeostasis is considered the initial step in treating ulcerative colitis. Plasma-activated solutions (PAS) are liquids rich in various reactive nitrogen species (RNS) and reactive oxygen species (ROS) and are used to treat multiple diseases. However, its effect on ulcerative colitis remains to be examined. Therefore, using a DSS-induced mice colitis model, it is found that PAS has the potential to treat colitis and prevent its recurrence by promoting intestinal mucosal repair, reducing inflammation, improving redox homeostasis, and reversing gut microbiota dysbiosis. Further, an equipment is designed for preparing PAS without using nitrogen; however, after treatment with the Nitro-free PAS, the therapeutic effect of PAS is significantly weakened or even lost, indicating that RNS may be the main mediator by which PAS exerts its therapeutic effects. Overall, this study demonstrates the treatment of ulcerative colitis as a novel application of PAS.

Low temperature plasma ablation device for minimally invasive surgery.

This study introduces the design principle of a high-frequency square wave power supply, as well as the simulation and design process of a minimally invasive electrosurgical scalpel, which formed the low temperature plasma in saline solution. In order to verify the performance of the device, saline discharge experiments and pork ablation experiments were performed. An alternating high-frequency square-wave voltage was applied between coaxial double-layer electrodes with a spacing of 400 µm. The waveforms and amplitude of output voltage and current, conductance between electrodes, and output power were measured in saline discharge experiments. The results of pork ablation experiments with different power sources demonstrate that the device can generate low-temperature plasma for ablation rather than relying on thermal effects. The device can ablate pork under the driving of a 10 V, 100 kHz square wave voltage. In addition, the ablation speed and area will be greater with an increase in voltage or frequency.

Mapping quantitative trait loci associated with callus browning in Dongxiang common wild rice (Oryza rufipogon Griff.).

BACKGROUND: Genetic transformation of indica rice (Oryza sativa ssp. indica) is limited by callus browning, which results in poor in vitro tissue culturability. Elucidating the genes in common wild rice (Oryza rufipogon Griff.) that control callus browning is fundamental for improving the tissue culturability of indica rice varieties. METHODS AND RESULTS: We used a population of 129 O. rufipogon (Dongxiang common wild rice; DXCWR) introgression lines in the elite cultivar GC2 (Oryza sativa ssp. indica) background and 159 simple sequence repeat (SSR) markers to identify quantitative trait loci (QTLs) associated with callus browning. We evaluated callus browning based on the indices of callus browning rate (CBR), callus browning index (CBI), and standard callus browning index (SCBI). CONCLUSIONS: We detected 30 QTLs associated with callus browning across all lines, mapping to chromosomes 1, 2, 3, 4, 8, 9, and 12. These genomic regions were repeatedly associated with differences in CBR, CBI, and SCBI. The alleles from DXCWR showed additive effects in reducing callus browning. We identified new QTLs near the markers RM247 and RM7003 on chromosome 12, indicating that these QTLs are unique to DXCWR. Furthermore, we identified six introgression lines with significantly lower callus browning. These lines will be useful germplasms for genetic transformation and fine-mapping of the culturability trait.

Abdominal ultrasonographic manifestations in pediatric patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disease which leads to formation of benign tumors in the brain and other organs of the body. Ultrasound (US) can detect the location, quantity, size and internal echo of TSC-associated renal diseases, liver angiomyolipoma (AML), and co-existing lesions, providing important diagnostic basis for clinical diagnosis. The aim of the present study was to investigate the abdominal ultrasonographic features of pediatric TSC and explore the advantages of abdominal ultrasonography in clinical practice. METHODS: Data of children with TSC, who presented to the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, between January 2016 and November 2018, were analyzed by a retrospective chart review. The cases were identified from electronic medical records (EMR) system and underwent ultrasonography, we yielded a total of 12 patients. RESULTS: The 12 pediatric patients, including 5 boys and 7 girls, ranged in age from 9 months to 13 years old. And they all had a history of epilepsy. All the patients underwent brain magnetic resonance imaging (MRI) or computed tomography (CT) examination, which revealed a scattered distribution of multiple hyperintense nodules. Of the 12 patients, 10 had TSC-associated bilateral renal AMLs, 5 had hepatic AML, and 4 had renal cysts. CONCLUSIONS: US is a useful and non-invasive tool for the detection of TSC-associated renal and liver lesions and for clinical follow-up among pediatric patients.

Decolorization effect and related mechanism of atmospheric pressure plasma jet on Eriochrome Black T.

In this study, Eriochrome Black T (EBT) in water was decolorized by means of argon atmospheric pressure plasma jet (APPJ), which showed great decolorization performance. The results showed that the relatively high decolorization rate (approximately 80%) was obtained after plasma treatment for 6 min. Changes to some reactive oxygen and nitrogen species (RONS) in the liquid phase were detected. The contents of peroxide, HO·, O2 -·, and NO· in the plasma-treated EBT solution were much less than those in the activated water. The roles of H2O2 and HO· in the decolorization of EBT solution were explored by evaluating the effects of their scavengers, and by exploring the direct effect of H2O2. The results indicated that reactive oxygen species (ROS), especially HO· and O2 -·, played significant roles in the decolorization of the EBT solution. Analysis of degradation by-products indicated that plasma discharge could destroy the azo bond first and gradually break the aromatic rings of EBT molecules into small molecular compounds.

Low-temperature Plasma Promotes Fibroblast Proliferation in Wound Healing by ROS-activated NF-κB Signaling Pathway.

Low-temperature plasma (LTP) has shown great promise in wound healing, although the underlying mechanism remains poorly understood. In the present study, an argon atmospheric pressure plasma jet was employed to treat L929 murine fibroblasts cultured in vitro and skin wounds in BALB/c mice. The in vitro analysis revealed that treatment of fibroblasts with LTP for 15 s resulted in a significant increase in cell proliferation, secretion of epidermal growth factor (EGF) and transforming growth factor-ßi (TGF-ßi), production of intracellular reactive oxygen species (ROS), and the percentage of cells in S phase, protein expression of phosphorylated p65 (P-p65) and cyclinD1, but a noted decrease in the protein expression of inhibitor kappa B (IκB). The in vitro experiments demonstrated that 30-s LTP treatment enhanced the number of fibroblasts and the ability of collagen synthesis, while 50-s treatment led to the opposite outcomes. These results suggested that LTP treatment promotes the fibroblast proliferation in wound healing by inducing the generation of ROS, upregulating the expression of P-p65, downregulating the expression of IκB, and activating the NF-κB signaling pathway and consequently altering cell cycle progression (increased DNA synthesis in S phage).

Low temperature plasma promoting fibroblast proliferation by activating the NF-κB pathway and increasing cyclinD1 expression.

The potential applications of low temperature plasma (LTP) in wound healing have aroused the concern of many researchers. In this study, an argon atmospheric pressure plasma jet was applied to generate LTP for treatment of murine fibroblast cell (L929) cultured in vitro to investigate the effect of NF-κB pathway on fibroblast proliferation. The results showed that, compared with the control, L929 cells treated with plasma for less than 20 s had significant increases of proliferation; the productions of intracellular ROS, O2- and NO increased with prolongation of LTP treatment time; NF-κB pathway was activated by LTP in a proper dose range, and the expression of cyclinD1 in LTP-treated cells increased with the same trend as cell proliferation. After RNA interference to block p65 expression, with the same treatment time, RNAi-treated cells proliferated more slowly and expressed less cyclinD1 than normal cells. Furthermore, pretreatment with N-acetyl-L-cysteine (NAC) markedly prevented the plasma-induced changes in cells. In conclusion, the proliferation of L929 cells induced by LTP was closely related to NF-κB signaling pathway, which might be activated by appropriate level of intracellular ROS. These novel findings can provide some theoretical reference of LTP inducing cell proliferation and promoting wound healing.

Dual effects of atmospheric pressure plasma jet on skin wound healing of mice.

Cold plasma has become an attractive tool for promoting wound healing and treating skin diseases. This article presents an atmospheric pressure plasma jet (APPJ) generated in argon gas through dielectric barrier discharge, which was applied to superficial skin wounds in BALB/c mice. The mice (n = 50) were assigned randomly into five groups (named A, B, C, D, E) with 10 animals in each group. Natural wound healing was compared with stimulated wound healing treated daily with APPJ for different time spans (10, 20, 30, 40, and 50 seconds) on 14 consecutive days. APPJ emission spectra, morphological changes in animal wounds, and tissue histological parameters were analyzed. Statistical results revealed that wound size changed over the duration of the experimental period and there was a significant interaction between experimental day and group. Differences between group C and other groups at day 7 were statistically significant (p < 0.05). All groups had nearly achieved closure of the untreated control wounds at day 14. The wounds treated with APPJ for 10, 20, 30, and 40 seconds showed significantly enhanced daily improvement compared with the control and almost complete closure at day 12, 10, 7, and 13, respectively. The optimal results of epidermal cell regeneration, granulation tissue hyperplasia, and collagen deposition in histological aspect were observed at day 7. However, the wounds treated for 50 seconds were less well healed at day 14 than those of the control. It was concluded that appropriate doses of cold plasma could inactivate bacteria around the wound, activate fibroblast proliferation in wound tissue, and eventually promote wound healing. Whereas, over doses of plasma suppressed wound healing due to causing cell death by apoptosis or necrosis. Both positive and negative effects may be related to the existence of reactive oxygen and nitrogen species (ROS and RNS) in APPJ.

[Inactivation of bacterial spores using low-temperature plasma].

OBJECTIVE: To investigate the effect of low-temperature plasma on inactivation of bacterial spores and explore the mechanism. METHODS: Dielectric barrier discharge (DBD) was employed to generate the atmospheric low-temperature plasma for treatment of B.subtilis var. niger spores with the gas spacing of 3, 4 and 5 and treatment time intervals of 5, 10, 15, 20, 25, 30 and 35 s. The survived colonies was counted with plate counting method, and the killing log value (KLV) at different treatment times was calculated. The inactivation effect of electric field on B.subtilis var.niger spores was also investigated and the spores treated with low-temperature plasma were observed with transmission electron microscope. RESULTS: With the gap spacing of 3, 4 and 5 mm, the KLV of low-temperature plasma on B.subtilis var.niger spores within 25, 30 and 35 s of exposure was more than 5. The germicidal effects of the electric field on B. subtilis var.niger spores were rather poor. Transmission electron microscopy demonstrated total destruction of the surface and interior structure of the spores by low-temperature plasma. CONCLUSIONS: Low-temperature plasma is effective for inactivation of the bacterial spores with a time and dose dependence. The penetrating effect of charged particles and oxygenation effect of the reactive oxygen species might play a dominant role in plasma-induced bacterial spore inactivation, while the role of electric field is negligible.