Effect and mechanism of terahertz irradiation in repairing spinal cord injury in mice.

SIGNIFICANCE: Spinal cord injury (SCI) represents a serious trauma to the central nervous system. Terahertz (THz) irradiation is an emerging technique, it has potential application prospects in the treatment of central nervous system diseases. AIM: We report on the investigation of the effect and mechanism of THz irradiation in repairing SCI in mice. APPROACH: The effect of THz in SCI was evaluated by the expression of inflammatory factors, the mouse behavioral scale (BMS), and immunofluorescence staining. After RNA sequencing (RNA-seq), we determined the differentially expressed genes (DEGs) and performed GO and KEGG analysis. RESULTS: After THz irradiation, the inflammatory response, the behavioral function, and the severity of SCI recovered well, indicating that THz irradiation can effectively promote the repair of SCI. GO and KEGG results show that genes related to inflammation, immune regulation, and IL-17 signaling pathway may play an important role in this process. CONCLUSIONS: THz irradiation can effectively promote the repair of SCI. Genes related to inflammation, immune regulation, and IL-17 signaling pathway may play an important role in this process.

Relationship between uric acid and cerebral amyloid angiopathy.

Purpose: To explored Relationship between uric acid and cerebral amyloid angiopathy; Materials and methods: ZO-1 and RAGE in HBMECs were detected by western blotting, and then, we analyzed ZO-1, occludin, and RAGE mRNA expression levels in different treatment groups using RTPCR. Cell counts and the relative αSMA fluorescence intensity were measured in order to evaluate the protective effect of uric acid against injury to HBVSMCs. Analysis of variance showed that LDH leakage rate was used to verify the uric acid protective effect on the injury induced by Aß1-40. After that, the level of uric acid in serum and Aß1-40 in brain tissue was analyzed by western blotting and immunohistochemistry to evaluate the protective effect of uric acid in the brain of APP23 mice. Meanwhile, Occludin, ZO-1, and RAGE protein levels were measured by western blotting; Results: Uric acid reduced the negative effects of Aß on the vascular endothelium and smooth muscle cells and protected the vascular wall in vitro. In APP23 mice, Aß1-40 and Aß1-42 levels were significantly elevated in brain tissues and further increased after uric acid concentration was decreased. In APP23 mice, ZO-1 and occludin expression levels were both significantly lower than those in wild-type animals. After uric acid concentration was lowered in APP23 mice, ZO-1 and occludin expression levels were significantly lower than those in untreated animals; Conclusions: Uric acid in the blood protects the blood vessels from CAA damage to the blood vessel wall, and reduces the occurrence of cerebral hemorrhage.

Cold Atmospheric Plasma Suppressed MM In Vivo Engraftment by Increasing ROS and Inhibiting the Notch Signaling Pathway.

Multiple myeloma (MM) is the second most common hematologic malignancy. MM stem cells (MMSCs) are thought to be the main causes of in vivo engraftment and eventual recurrence. As a notable new technology, cold atmospheric plasmas (CAPs) show a promising anti-tumor effect, due to their production of various ROS. In this study, we found that different types of plasma could inhibit MM's ability to form cell colonies, suppress MM in vivo engraftment, and extend survival times. We demonstrated that NAC (a ROS scavenger) could block ROS increases and reverse the inhibition of MM's cell-colony-formation ability, which was induced by the plasma treatment. By using a stem cell signaling array, we found that the Notch pathway was inhibited by the plasma treatment; this was further confirmed by conducting real-time PCRs of three MM cell lines. Together, these results constitute the first report of plasma treatment inhibiting MM in vivo engraftment and prolonging survival time by suppressing the Notch pathway via ROS regulation.

In Vivo Metabolic Analysis of the Anticancer Effects of Plasma-Activated Saline in Three Tumor Animal Models.

In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in vivo. In addition, based on an ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) analysis of tumor cell metabolism, the glycerophospholipid metabolic pathway was the most susceptible metabolic pathway to PAS treatment in melanoma in vitro and in vivo. Furthermore, PAS also inhibited cell proliferation in vivo in oral tongue squamous-cell cancer and non-small-cell lung cancer. There were few toxic side effects in the three animal models, and the treatment was deemed safe to use. In the future, plasma-activated liquids may serve as a potential therapeutic approach in the treatment of cancer.

Behavioral Effect of Terahertz Waves in C57BL/6 Mice.

Terahertz is a new radiation source with many unique advantages. In recent years, its application has rapidly expanded to various fields, but there are few studies on the individual effects of terahertz. In this study, we investigated the behavioral effects of terahertz radiation on C57BL/6 mice, and we conducted an open field test, an elevated plus maze test, a light-dark box test, a three-chamber social test, and a forced swim test to explore the effects of terahertz radiation on mice from a behavioral perspective. The results show that terahertz wave may increase anti-anxiety, anti-depression, and social interaction in mice.

Plasma-activated thermosensitive biogel as an exogenous ROS carrier for post-surgical treatment of cancer.

Post-surgical residual tumor cells are the primary cause of relapse and progression of cancer but unfortunately, there are limited therapeutic options. In this work, a fillable plasma-activated biogel is produced on a thermosensitive biogel [(Poly-DL-lactide)-(poly-ethylene glycol)-(poly-DL-lactide), PLEL] with the aid of a discharge plasma for local post-operative treatment of cancer. In vivo data show that the plasma-activated PLEL biogel (PAPB) eliminates residual tumor tissues after removal surgery and also inhibits in situ recurrence while showing no evident systemic toxicity. Moreover, the PAPB possesses excellent storage capability, allows for slow release of plasma-generated reactive oxygen species (ROS), and exhibits good ROS-mediated anticancer effects in vitro. Our results reveal that the novel plasma-activated biogel is an effective therapeutic agent for local post-operative treatment of cancer.

Effect of He Plasma Jet Versus Surface Plasma on the Metabolites of Acute Myeloid Leukemia Cells.

Cold atmospheric plasma, including plasma jet and surface plasma, can promote the apoptosis of cancer cells without causing significant damage to surrounding normal cells, which was hopeful to be applied to the clinical cancer therapy. However, experimental plasma devices used directly to clinical experiments has challenges in technology and methods, especially the difference in killing tumor cells efficiency of these two common plasma sources. Therefore, it is great necessity to explore the differences in treating tumors between different plasma sources. This paper achieved good killing efficiency by using two kinds of cold atmospheric plasma generating devices, namely plasma jet and surface plasma treatment along acute myeloid leukemia (AML). The results showed that the He plasma jet kills leukemia cells more efficiently than surface plasma with the same voltage and frequency and the same time. By GC-TOFMS and metabolomics analysis, this paper compared the differential metabolites of leukemia cells treated by two plasma devices and the key metabolic pathways closely related to differential metabolites. Simultaneously, we found alanine, aspartate and glutamate metabolism was most correlated with a key differential metabolite, glutamine. It was found that the glutaminase activity of He plasma jet group was lower than that of surface plasma group, which might be a reason for He plasma jet group to kill tumor cells better. It was also worth noting that relative quantity of glucose metabolites of plasma jet treatment group was lower than that of surface plasma treatment group. This study provides the basis for clinical trials for future.

The Antitumor Effects of Plasma-Activated Saline on Muscle-Invasive Bladder Cancer Cells In Vitro and In Vivo Demonstrate Its Feasibility as a Potential Therapeutic Approach.

Muscle-invasive bladder cancer (MIBC) is a fast-growing and aggressive malignant tumor in urinary system. Since chemotherapy and immunotherapy are only useable with a few MIBC patients, the clinical treatment of MIBC still faces challenges. Here, we examined the feasibility of plasma-activated saline (PAS) as a fledgling therapeutic strategy for MIBC treatment. Our data showed that plasma irradiation could generate a variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in saline. In vivo tests revealed that pericarcinomatous tissue injection with PAS was effective at preventing subcutaneous bladder tumor growth, with no side effects to the visceral organs after long-term administration, as well as having no obvious influence on the various biochemistry indices of the blood in mice. The in vitro studies indicated that adding 30% PAS in cell culture media causes oxidative damage to the bladder transitional cells T24 and J82 through enhancing the intracellular ROS level, and eventually induces cancer cells' apoptosis by activating the ROS-mediated Fas/CD95 pathway. Therefore, for an intracavity tumor, these initial observations suggest that the soaking of the tumor tissue with PAS by intravesical perfusion may be a novel treatment option for bladder cancer.

Aberrant Expressional Profiling of Small RNA by Cold Atmospheric Plasma Treatment in Human Chronic Myeloid Leukemia Cells.

Small RNAs (sRNAs), particularly microRNAs (miRNAs), are functional molecules that modulate mRNA transcripts and have been implicated in the etiology of various types of cancer. Cold atmospheric plasma (CAP) is a physical technology widely used in the field of cancer treatment after exhibiting extensive lethality on cancer cells. However, few studies have reported the exact role of miRNAs in CAP-induced anti-cancer effects. The aim of the present study was to determine whether miRNAs are involved in CAP-induced cytotoxicity by using high-throughput sequencing. Our research demonstrated that 28 miRNAs were significantly changed (17 upregulated and 11downregulated) following 24 h of treatment with a room-temperature argon plasma jet for 90 s compared with that of the untreated group in human chronic myeloid leukemia K562 cells. GO enrichment analysis revealed that these target genes were related to cell organelles, protein binding, and single-organism processes. Furthermore, KEGG pathway analysis demonstrated that the target genes of differentially expressed miRNAs were primarily involved in the cAMP signaling pathway, AMPK signaling pathway, and phosphatidylinositol signaling system. Taken together, our study demonstrated that CAP treatment could significantly alter the small RNA expression profile of chronic myeloid leukemia cells and provide a novel theoretical insight for elucidating the molecular mechanisms in CAP biomedicine application.

Effects of Plasma-Activated Water on Skin Wound Healing in Mice.

Cold atmospheric plasma (CAP) has been widely used in biomedicine during the last two decades. While direct plasma treatment has been reported to promote wound healing, its application can be uneven and inconvenient. In this study, we first activated water with a portable dielectric barrier discharge plasma device and evaluated the inactivation effect of plasma-activated water (PAW) on several kinds of bacteria that commonly infect wounds. The results show that PAW can effectively inactivate these bacteria. Then, we activated tap water and examined the efficacy of PAW on wound healing in a mouse model of full-thickness skin wounds. We found that wound healing in mice treated with PAW was significantly faster compared with the control group. Histological analysis of the skin tissue of mice wounds showed a significant reduction in the number of inflammatory cells in the PAW treatment group. To identify the possible mechanism by which PAW promotes wound healing, we analyzed changes in the profiles of wound bacteria after PAW treatment. The results show that PAW can significantly reduce the abundance of wound bacteria in the treatment group. The results of biochemical blood tests and histological analysis of major internal organs in the mice show that PAW had no obvious side effects. Taken together, these results indicate that PAW may be a new and effective method for promoting wound healing without side effects.

Analysis of Metabolite Profiling in Human Endothelial Cells after Plasma Jet Treatment.

Cold atmospheric plasma (CAP) is a novel technology, which has been widely applied in biomedicine, especially in wound healing, dermatological treatment, hemostasis, and cancer treatment. In most cases, CAP treatment will interact with innumerable blood capillaries. Therefore, it is important and necessary to understand the effects of CAP treatment on endothelial cell metabolism. In this study, the metabolite profiling of plasma treatment on endothelial cells was measured by gas chromatography tandem time-of-flight mass spectrometry (GC-TOF-MS). We found that 695 signals (metabolites) were detected by GC-TOF-MS and then evaluated using orthogonal projections to latent structures discriminant analysis (OPLS-DA). All the differential metabolites were listed, and proline and xanthosine were the two of the most downregulated metabolites by plasma treatment. By comprehensive metabolic pathway analysis with the KEGG pathway, we showed that alanine, aspartate, glutamate, and purine metabolism pathways were the most significantly suppressed after gas plasma treatment in human endothelial cells. Our finding gives an overall picture of the metabolic pathways affected by plasma treatment in endothelial cells.

Inverse design of multifunctional plasmonic metamaterial absorbers for infrared polarimetric imaging.

Metamaterial absorbers, consisting of assembling arrays of optical resonators with subwavelength dimensions and spacing, allow efficiently absorption electromagnetic radiation by leveraging the strong electrical and magnetic resonances. Beyond the enhanced absorption, there is a growing interest to realize multi-functional absorbers, for example, absorbers with extended bandwidth, strong polarization extinction ratio, to name a few. Traditionally, designing multi-functional absorbers require complex brute-force optimizations with sizable parameter space, which turn out to be rather inefficient. Here, using the particle swarm optimization algorithm, we design and experimentally demonstrate broadband and highly polarization selective mid-IR metal-insulator-metal absorbers, covering the technologically important 3-5 µm atmospheric transparency band. With spectrally averaged absorption exceeding 70%, a high polarization extinction ratio of 40.6 is concurrently achieved by the algorithm. We also investigate the incident angle dependence of the spectral absorption and clarify the origin of optical losses. By integrating with the growing range of mid-IR detectors and imagers, our devices can enable new applications such as mid-IR full Stokes imaging polarimetry for remote sensing.

Effect of cold atmospheric plasma treatment on the metabolites of human leukemia cells.

BACKGROUND: Acute myeloid leukemia (AML) is a typically fatal malignancy and new drug and treatment need to be developed for a better survival outcome. Cold atmospheric plasma (CAP) is a novel technology, which has been widely applied in biomedicine, especially in various of cancer treatment. However, the changes in cell metabolism after CAP treatment of leukemia cells have been rarely studied. METHODS: In this study, we investigated the metabolite profiling of plasma treatment on leukemia cells based on Gas Chromatography Tandem Time-of-Flight Mass Spectrometry (GC-TOFMS). Simultaneously, we conducted a series of bioinformatics analysis of metabolites and metabolic pathways with significant differences after basic data analysis. RESULTS: 800 signals were detected by GC-TOF mass-spectrometry and then evaluated using PCA and OPLS-DA. All the differential metabolites were listed and the related metabolic pathways were analyzed by KEGG pathway. The results showed that alanine, aspartate and glutamate metabolism had a significant change after plasma treatment. Meanwhile, d-glutamine and d-glutamate metabolism were significantly changed by CAP. Glutaminase activity was decreased after plasma treatment, which might lead to glutamine accumulation and leukemia cells death. CONCLUSIONS: We found the above two metabolic pathways vulnerable to plasma treatment, which might result in leukemia cells death and might be the cornerstone of further exploration of plasma treatment targets.

Plasma enhance drug sensitivity to bortezomib by inhibition of cyp1a1 in myeloma cells.

BACKGROUND: Drug resistance is one of the major problems encountered in clinical therapy of multiple myeloma treatment. Combination treatment with several drugs may increase the sensitivity and overcome drug resistance. METHODS: Here, we combined chemotherapy with a newly developed technology, cold atmospheric plasma, to enhance drug sensitivity. RESULTS: We found that plasma treatment had a synergistic anti-cancer effect with a first line drug (bortezomib). Based on our previous study, we further found that plasma treatment could inhibit Notch pathway and down-regulate cyp1a1 expression and enzyme activity, which contributing to the enhanced drug sensitivity to bortezomib after combination of bortezomib with gas plasma. CONCLUSIONS: Our results showed a new strategy to overcome drug resistance by combination of traditional chemotherapy with cold atmospheric plasma.

Cold atmospheric plasma induces apoptosis of melanoma cells via Sestrin2-mediated nitric oxide synthase signaling.

Cold atmospheric plasma (CAP) represents a promising therapy for selectively cancer killing. However, the mechanism of CAP-induced cancer cell death remains unclear. Here, we identified the tumor necrosis factor-family members, especially Fas, and overloaded intracellular nitric oxide participated in CAP induced apoptosis in A375 and A875 melanoma cell lines, which was known as extrinsic apoptosis pathway. This progress was mediated by antagonistic protein of reactive oxygen species, Sestrin2. The over expression of Sestrin2 induced by plasma treatment resulted in phosphorylation of p38 mitogen-activated protein kinase (MAPK), followed by increased expression of nitric oxide synthase (iNOS), Fas and Fas ligand. Depletion of Sestrin2 reduced iNOS and Fas expression, which was associated with reduction of plasma-induced apoptosis. In contrast, inhibition of iNOS activity and phosphorylation of p38 did not alter Sestrin2 expression in plasma-treated melanoma cells. Taken together, cold atmospheric plasma increases Sestrin2 expression and further activates downstream iNOS, Fas and p38 MAPK signaling to induce apoptosis of melanoma cell lines. These findings suggest a previously unrecognized mechanism in melanoma cells response to cold atmospheric plasma therapy.

Acoustic manipulation of particles in a cylindrical cavity: Theoretical and experimental study on the effects of boundary conditions.

Precise manipulation of microparticles in microchannels is a primary technique for numerous lab-on-a-chip bioengineering research and applications, as it determines the chip's functions and analytical results. Acoustic manipulation, using the acoustic radiation force, is a compact, versatile and contactless manipulation technique, which can be easily integrated with other microfluidic components. It is our main purpose to report the effect of boundary condition of a cylindrical microfluidic cavity on the acoustic particles' manipulation. A device consisting of a cylindrical cavity in a silicon wafer with three kinds of top boundary conditions (rigid, soft, and imperfect rigid boundary) has been built. The corresponding distributions of acoustic radiation force are analyzed analytically and numerically. Experiments are performed with 2.5 µm radius polystyrene microspheres in the cavity covered by three reflective layers (340 µm-thick glass, 400 µm-thick PDMS, and 660 µm-thick glass film), respectively, which specify the three different boundary conditions at the top of the cavity. It is demonstrated that the boundary condition of a cavity influences the acoustic radiation force and the stable positions of particles, and this is in agreement with the theoretical predictions. Thus, the effects of boundary conditions need to be considered for precise acoustic manipulation.

Cold atmospheric plasma as a potential tool for multiple myeloma treatment.

Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O2 plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response to plasma treatment. Furthermore, p53 is shown to be a key transcription factor in activating CD95 and caspase cascades. More importantly, we demonstrate that CD95 expression is higher in tumor cells than in normal cells in both MM cell lines and MM clinical samples, which suggests that CD95 could be a favorable target for plasma treatment as it could selectively inactivate myeloma tumor cells. Our results illustrate the molecular details of plasma induced myeloma cell apoptosis and it shows that gas plasma could be a potential tool for myeloma therapy in the future.

Alteration of metabolite profiling by cold atmospheric plasma treatment in human myeloma cells.

BACKGROUND: Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet. METHODS: In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG analysis we try to figure out the metabolism pathway that was significantly affected by gas plasma treatment. RESULTS: By GC-TOF mass-spectrometry, 573 signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we listed all the differential metabolites and further classified into different metabolic pathways. The results showed that beta-alanine metabolism pathway was the most significant change after He gas plasma treatment in myeloma cells. Besides, propanoate metabolism and linoleic acid metabolism should also be concerned during gas plasma treatment of cancer cells. CONCLUSIONS: Cold atmospheric plasma treatment could significantly alter the metabolite profiling of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the most susceptible to He gas plasma treatment.

Identification of potential therapeutic target genes and miRNAs for primary myelofibrosis with microarray analysis.

The aim of the present study was to identify potential therapeutic target genes and miRNAs for primary myelofibrosis (PMF). The dataset GSE53482 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) of peripheral blood (PB) cluster of differentiation (CD)34+ cells from PMF patients (PB-PMF group) and peripheral blood CD34+ cells from healthy individuals (PB-control group) were analyzed using the Linear Models for Microarray Data package in R. The Kyoto Encyclopedia of Genes and Genomes was used for pathway enrichment analysis. MiRNA-gene joint enrichment analysis was performed by ENViz and a miRNAs-gene regulatory network was constructed. A total of 1,182 DEGs (773 upregulated and 109 downregulated) and 48 DEMs (28 upregulated and 20 downregulated) were identified. According to the pathway enrichment analysis, a number of DEGs were enriched in metabolic pathways, including IDH1 and DNMT1. Other DEGs were enriched in the citrate cycle (tricarboxylic acid cycle; IDH1 and IDH3A) and certain DEGs were enriched in pyrimidine metabolism, including CARD8. For downregulated genes, certain DEGs were enriched in the spliceosome, including SF3B1 and CDC40. Furthermore, hsa-miR-127-3p, hsa-miR-140-3p and hsa-miR345 were associated with cell cycle-related biological processes, signal transduction and cell surface receptor signaling pathway. The DEM-DEG regulatory network indicated that hsa-miR-543 regulated 113 genes, including CARD8 and TIFA. The present study identified a number of genes, including IDH1, DNMT1, SF3B1 and CARD8, and miRNAs, including hsa-miR-127-3p and hsa-miR-140-3p, which may be therapeutic targets in the treatment of PMF.

Investigation of crucial genes and microRNAs in conventional osteosarcoma using gene expression profiling analysis.

The present study aimed to screen potential genes associated with conventional osteosarcoma (OS) and obtain further information on the pathogenesis of this disease. The microarray dataset GSE14359 was downloaded from the Gene Expression Omnibus. A total of 10 conventional OS samples and two non­neoplastic primary osteoblast samples in the dataset were selected to identify the differentially expressed genes (DEGs) using the Linear Models for Microarray Data package. The potential functions of the DEGs were predicted using Gene Ontology (GO) and pathway enrichment analyses. Protein­protein interaction (PPI) data were also obtained using the Search Tool for the Retrieval of Interacting Genes database, and the PPI network was visualized using Cytoscape. Module analysis was then performed using the Molecular Complex Detection module. Additionally, the potential microRNAs (miRNAs) for the upregulated DEGs in the most significant pathway were predicted using the miRDB database, and the regulatory network for the miRNAs­DEGs was visualized in Cytoscape. In total, 317 upregulated and 670 downregulated DEGs were screened. Certain DEGs, including cyclin­dependent kinase 1 (CDK1), mitotic arrest deficient 2 like 1 (MAD2L1) and BUB1 mitotic checkpoint serine/threonine­protein kinase (BUB1), were significantly enriched in the cell cycle phase and oocyte meiosis pathway. DEGs, including replication factor C subunit 2 (RFC2), RFC3, RFC4 and RFC5, were significantly enriched in DNA replication and interacted with each other. RFC4 also interacted with other DEGs, including CDK1, MAD2L1, NDC80 kinetochore complex and BUB1. In addition, RFC4, RFC3 and RFC5 were targeted by miRNA (miR)­802, miR­224­3p and miR­522­3p. The DEGs encoding RFC may be important for the development of conventional OS, and their expression may be regulated by a number of miRNAs, including miR­802, miR­224­3p and miR­522­3p.