Cold atmospheric plasma attenuates skin cancer via ROS induced apoptosis.

BACKGROUND: Cold atmospheric plasma (CAP) has been widely used in biomedical research, especially in vitro cancer therapy. Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. However, the mechanism of CAP therapy on CSCC remains unclear. METHODS AND RESULTS: The animal models of CSCC induced by 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) were constructed. For the CAP treatment group, after each TPA application, CAP was administered for 3 min twice weekly after drying. HE staining were used to detect the pathological status of tumor tissue in each group. The levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 were evaluated by western blot and qPCR. TUNEL staining were used to detect apoptosis in tumor tissues. In vivo, serum samples were used for ELISA of total ROS. MTT assay was used to detect the viability of A431 cells. Western blot and qPCR were used to detect the levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 in A431 cells. A431 cell proliferation was examined by colony formation assay. The proportions of apoptosis of A431 cells were detected by flow cytometry. Transwell assessed the ability of A431 cells migration and proliferation. We found that CAP could induce skin cancer cells apoptosis and inhibit the progress of skin cancer. Through experiments in vitro, reactive oxygen species (ROS) generated by N-acetylcysteine (NAC) and CAP inhibited the proliferation and migration of A431 skin cancer cells while promoting apoptosis. CONCLUSIONS: These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.

[Screening value and correlation of body measurement indices for metabolic syndrome in the population undergoing physical examinations in Chengdu during 2018-2020].

OBJECTIVE: To investigate the screening value and correlation of body measurement indicators for metabolic syndrome(MS) and to provide evidence for MS screening. METHODS: Through a cross-sectional research approach, data from individuals aged 18 and above who participated in health examinations at the North Health Management Center of Sichuan Provincial People's Hospital from 2018 to 2020 were reviewed. Data including height, weight, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking history, and alcohol consumption history were collected. Subsequently, a body shape index(ABSI), body roundness index(BRI), body adiposity index(BAI), abdominal volume index(AVI), relative fat mass index(RFM), and body mass index(BMI) were computed. The individuals were then divided into MS and non-MS groups. The value of body measurement indices in screening for MS in the population aged 18 and above was assessed using ROC curves. Regression analysis was employed to explore the correlation between body measurement indices and MS. RESULTS: A total of 73 411 valid health examination data were obtained, including 44 426 males and 28 985 females. The MS group comprised 9181 males(21%) and 1668 females(6%). In the comparison between the MS and non-MS groups, there were statistically significant differences in ABSI((0.08±0.00) vs. (0.08±0.00)), BRI((4.95±0.67) vs. (4.17±0.68)), BAI((28.08±3.52) vs. (26.39±3.39)), AVI((17.51±2.77) vs. (12.85±2.91)), BMI((27.15±2.99) vs. (23.00±3.04)) and RFM((29.77±5.35) vs. (27.13±6.39))(P<0.05). Univariate Logistic regression analysis showed that ABSI(OR=2.303, 95%CI 1.190-4.457), BRI(OR=4.596, 95%CI 4.446-4.752), BAI(OR=1.144, 95%CI 1.137-1.151), AVI(OR=1.668, 95%CI 1.652-1.684), RFM(OR=1.067, 95%CI 1.064-1.071) and BMI(OR=1.516, 95%CI 1.503-1.528) were associated with MS(P<0.05). Multifactorial Logistic regression analysis corrected for sex, age, smoking and alcohol consumption showed that ABSI(OR=1.767, 95% CI 4.237-7.371), BRI(OR=5.441, 95% CI 5.228-5.663), BAI(OR=1.269, 95% CI 1.260-1.279), AVI(OR=1.648, 95% CI 1.631-1.665), RFM(OR=1.504, 95% CI 1.491-1.517) and BMI(OR=1.508, 95% CI 1.495-1.522) were associated with MS(P<0.05). The ROC curve analysis showed that in adults, the AVI had the highest screening value for MS in males(AUC=0.855, optimal cutoff value=16.18), followed by RFM(AUC=0.844, optimal cutoff value=25.71), BMI(AUC=0.811, optimal cutoff value=25.21), BRI(AUC=0.793, optimal cutoff value=4.39), BAI(AUC=0.709, optimal cutoff value=25.88), and ABSI(AUC=0.671, optimal cutoff value=0.08). In adult females, the RFM had the highest screening value for MS(AUC=0.918, optimal cutoff value=37.01), followed by AVI(AUC=0.911, optimal cutoff value=13.43), BRI(AUC=0.901, optimal cutoff value=4.71), BMI(AUC=0.860, optimal cutoff value=23.94), ABSI(AUC=0.804, optimal cutoff value=0.08), and BAI(AUC=0.797, optimal cutoff value=29.92). CONCLUSION: ABSI, BRI, BAI, AVI, BMI and RFM are all capable of screening for MS. Among males, AVI has the highest screening value for MS, followed by RFM, BMI, BRI, BAI and ABSI. Among females, RFM has the highest screening value for MS, followed by AVI, BRI, BMI, ABSI and BAI. ABSI, BRI, BAI, AVI, RFM and BMI are positively correlated with MS.

Low temperature plasma suppresses proliferation, invasion, migration and survival of SK-BR-3 breast cancer cells.

BACKGROUND: Low temperature plasma (LTP) is a developing field in recent years to play important roles of sterilization, material modification and wound healing. Breast cancer is a common gynecological malignant tumor. Recent studies have shown that LTP is a promising selective anti-cancer treatment. The effect of LTP on breast cancer is still unclear. In this study, We treated breast cancer cell lines with low temperature plasma for different periods of time and analyzed the relevant differences. METHODS AND RESULTS: SK-BR-3 cell nutrient solution was firstly treated by ACP for 0, 10, 20, 40, 80 and 120 s, which was next used to cultivateSK-BR-3cells for overnight.we found that LTP was able to suppress cell vitality, proliferation, invasion and migration of SK-BR-3 cells. Also, SK-BR-3 apoptosis was induced by LTP in a time-dependent manner. CONCLUSION: These evidences suggest the negative effect of LTP on malignant development of SK-BR-3 cells, and LTP has the potential clinical application for breast cancer treatment.

Cold Plasma Irradiation Attenuates Atopic Dermatitis via Enhancing HIF-1α-Induced MANF Transcription Expression.

Cold atmospheric plasma has been widely applied in medical treatment clinically, especially skin diseases. However, the mechanism of cold atmospheric plasma on the treatment of skin diseases is still undefined. In this study, dinitrofluorobenzene-induced atopic dermatitis mice model was constructed. Cold atmospheric plasma was able to decrease skin cells apoptosis, relieve skin inflammation, ER stress and oxidative stress caused by dinitrofluorobenzene stimulation, which was mediated by cold atmospheric plasma-induced MANF expression. In terms of mechanism, hypoxia-inducible factor-1α expression was increased intracellularly after cold atmospheric plasma treatment, which further bound to the promoter region of manf gene and enhanced MANF transcriptional expression. This study reveals that cold atmospheric plasma has a positive effect on atopic dermatitis treatment, also demonstrates the regulatory mechanism of cold atmospheric plasma on MANF expression via HIF-1α, which indicates the potential medical application of cold atmospheric plasma for atopic dermatitis treatment.

Effect of profilin-1 on the asymmetric dimethylarginine-induced vascular lesion-associated hypertension.

Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin-1, an actin-binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin-1 in ADMA-induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty-two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin-1 small hairpin RNA to interrupt the expression of profilin-1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin-1 was tested using real-time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin-1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p < 0.05). In vitro, studies showed ADMA-induced profilin-1 expression in a concentration- and time-dependent manner in RASMCs (p < 0.05), concomitantly with promoting the proliferation of RASMCs. Furthermore, ADMA-mediated proliferation of RASMCs and upregulation expression of profilin-1 were inhibited by blockade of the JAK2/STAT3 pathway or knockdown of profilin-1. Profilin-1 implicated in the ADMA-mediated vascular lesions in hypertension.

Cold Plasma Irradiation Regulates Inflammation and Oxidative Stress in Human Bronchial Epithelial Cells and Human Non-Small Cell Lung Carcinoma.

Atmospheric pressure cold plasma has shown multiple biological effects of anti-bacteria and anti-cancer. In this study, the effect of atmospheric pressure cold plasma on respiratory inflammation and oxidant stress is explored. Tunicamycin was used to stimulate human bronchial epithelial cells (HBECs) and A549 cells for inflammatory response and oxidative stress, followed by atmospheric pressure cold plasma treatment. For HBECs and A549 cells, atmospheric pressure cold plasma was able to alleviate tunicamycin-induced cell proliferation inhibition, inflammation and oxidant stress, and enhance nuclear factor-erythroid-2-related factor 2 (NRF2) pathway activation. Moreover, NRF2/ARE (anti-oxidant response elements) pathway was involved in the regulation of atmospheric pressure cold plasma on tunicamycin-induced oxidative stress. These results suggest the positive effect of atmospheric pressure cold plasma on inflammation and oxidant stress of respiratory system, indicating the therapeutic potential of atmospheric pressure cold plasma for respiratory diseases.

Modelling the symmetrical and asymmetrical effects of global oil prices on local food prices: A MENA region application.

This paper explores the complex nexus between the global oil prices and the food prices of the Middle East and North Africa (MENA) region during the period 2000-2020. Both linear and nonlinear models of the autoregressive distributed lag (ARDL) approach are adapted into panel data form to investigate the symmetrical and asymmetrical influence of oil prices on food prices. The key results are summarized: (i) the long-term effect of oil prices on food prices is significantly positive including both oil-exporting and oil-importing nations. The positive impact on oil exporters-due to higher oil revenues-is greater than importing nations, leading to an increased demand for food. Additionally, the effect on oil exporters is negative and significant in the short term but not significant for importers. (ii) The nonlinear ARDL panel analysis for the whole MENA sample confirms the presence of negative short-term asymmetric behaviour due to the heterogeneous response within the oil-importing and oil-exporting samples, while in the long term, the asymmetric effect is positive, indicating that food prices increase regardless of fluctuations in oil prices. (iii) The nonlinear ARDL results using time series affirm the absence of an asymmetric nexus among oil and food prices for some oil-exporting nations (including Kuwait, Saudi Arabia, United Arab Emirates) and Tunisia within the oil-importing group. However, the food prices of other countries are asymmetric to the oil price. This study provides recommendations that are useful to MENA countries to establish a stable mechanism for oil and food prices to ensure food security in the region.

Brugada syndrome associated with out-of-hospital cardiac arrest: A case report.

BACKGROUND: Brugada syndrome (BrS) is an inherited disease characterized by an electrocardiogram (ECG) with a coved-type ST-segment elevation in the right precordial leads (V1-V3), which predisposes to sudden cardiac death (SCD) due to polymorphic ventricular tachycardia or ventricular fibrillation in the absence of structural heart disease. We report the case of a 29-year-old man with out-of-hospital cardiac arrest. BrS is associated with a high incidence of SCD in adults, and increasing the awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving. CASE SUMMARY: A 29-year-old man suffered from out-of-hospital cardiac arrest, and after defibrillation, his ECG demonstrated a coved-type elevated ST segment in V1 and V2. These findings were compatible with type 1 Brugada pattern, and ECG of his brother showed a type 2 Brugada pattern. The diagnosis was BrS, NYHF IV, multiple organ dysfunction syndrome, sepsis, and hypoxic ischemic encephalopathy. The patient had no arrhythmia episodes after discharge throughout a follow-up period of 36 mo. CONCLUSION: Increasing awareness of BrS and prompt recognition of the Brugada ECG pattern can be lifesaving.

LINC00565 promotes proliferation and inhibits apoptosis of gastric cancer by targeting miR-665/AKT3 axis.

BACKGROUND: Numerous studies have shown that long noncoding RNA (lncRNA) is involved in gastric cancer (GC). A relevant microarray containing gastric cancer-related lncRNAs was downloaded from The Cancer Genome Atlas database. METHODS: qRT-PCR was used to analyze LINC00565 and AKT3 expression in tumor tissues and cell lines. Proliferative, colony formation and apoptotic abilities of GC cells after transfection of sh-LINC00565 were determined by CCK-8, colony formation assay and flow cytometry, respectively. RIP was enrolled to detect the interaction between LINC00565, AKT3 and miR-665. Dual luciferase assay was used to confirm the relation between miR-665 and LINC00565 and AKT3. RESULTS: Expression level of LINC00565 in GC tissue was highly expressed in GC, which was negatively correlated to prognosis of GC patients. The results showed that knockdown of LINC00565 decreased proliferative and colony formation abilities, and induced apoptosis of GC cells. Pearson analysis showed that LINC00565 was positively correlated with AKT3. Besides, AKT3 was significantly up-regulated in GC. In addition, knockdown of LINC00565 down-regulated AKT3. In order to explore the mechanism, we found that miR-665 could bind to LINC00565 by bioinformatics. Dual-luciferase reporter gene assay and RIP assay both verified the binding relationship between miR-665 and AKT3. Finally, rescue experiments were carried out to explore whether AKT3 could reverse the anti-cancer effect of low-level LINC00565 on GC development. CONCLUSION: In summary, the expression of LINC00565 is upregulated in GC. LINC00565 can be used as the sponge of miR-665 to up-regulate the expression of AKT3, thus promoting the progression of GC.

Targeting Nrf2-mediated heme oxygenase-1 enhances non-thermal plasma-induced cell death in non-small-cell lung cancer A549 cells.

Non-thermal plasma (NTP) treatment has been proposed as a potential approach for cancer therapy for killing cancer cells via generation of reactive oxygen species (ROS). As an antioxidant protein, Heme oxygenase-1 (HO-1) has been known to protect cells against oxidative stress. In this paper, we investigated the role of HO-1 activation in NTP-induced apoptosis in A549 cells. Distinctly increased ROS production and apoptosis were observed after NTP exposure. NTP exposure induced HO-1 expression in a dose- and time-dependent manner via activating the translocation of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) from cytoplasm to nucleus. Furthermore, inhibiting HO-1 activation with its specific inhibitor, ZnPP, increased "killing" effect of NTP. Knocking down HO-1 or Nrf2 with the special siRNA also led to elevated ROS level and enhanced NTP-induced cell death. In addition, the c-JUN N-terminal kinase (JNK) signaling pathway was shown to be involved in NTP-induced HO-1 expression. Interestingly, a higher resistance to NTP exposure of A549 cell compared to H1299 and H322 cells was found to be linked to its higher basal level of HO-1 expression. These findings revealed that HO-1 could be considered as a potential target to improve the effect of NTP in cancer therapy.

Hypericin-photodynamic therapy inhibits proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A.

OBJECTIVES: To elucidate the effects and potential mechanisms of hypericin-photodynamic therapy (HYP-PDT) for treating the human rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) MH7A cell-line. MATERIALS AND METHODS: MH7A cells were subjected to HYP-PDT intervention and apoptosis was evaluated via MTT, nuclear staining, and flowcytometry analyses. Intracellular reactive oxygen species (ROS) were measured with the fluorescent probe 2'7'-dichlorofluorescein diacetate (DCFH-DA). To verify the effects of HYP on apoptotic and nuclear factor kappa-B (NF-κB) pathways, caspase-8, 9, poly-ADP-ribose polymerase (PARP), phosphorylated (p)-NF-κB p65, NF-κB p65 and p-IκBα protein expressions were quantified with Western blot. Quantitative real-time PCR was used to assay NF-κB p65 mRNA. RESULTS: HYP-PDT inhibited MH7A cell viability and induced apoptosis in a dose-dependent manner. Meanwhile, intracellular ROS levels increased significantly after HYP-PDT treatment. Furthermore, the expression of cleaved caspase-9 and PARP was increased by HYP-PDT treatment, with a concurrent decline in NF-κB. CONCLUSION: HYP-PDT induces apoptosis in MH7A cells, at least partially, via generation of ROS, regulation of the apoptotic pathway and suppression of the NF-κB pathway. These findings suggest that HYP-PDT may be a potential treatment for RA.

[Temporary ectopic implantation of amputated fingers and dorsalis pedis flaps for thumb reconstruction and skin defect repair of hands].

OBJECTIVE: To investigate the feasibility of temporary ectopic implantation of amputated fingers and dorsalis pedis flaps for thumb reconstruction and skin defect repair of the hand. METHODS: Between February 2006 and February 2012, 9 patients with thumb amputation having no replanted condition were treated. There were 7 males and 2 females with an average age of 35 years (range, 20-45 years). The injury causes included explosive injury in 1 case, puncher injury in 1 case, stiring machine injury in 1 case, gear injury in 3 cases, and heavy pound injury in 3 cases. At 2-5 hours after injury, one-stage temporary ectopic implantation of amputated finger to foot was performed. After debridement, thumb defect was rated as degree III in 1 case, as degree IV in 3 cases, and as degree V in 5 cases. When amputated fingers survived completely after 1-4 months, the amputated finger was replanted to its anatomic position, skin defect was repaired with dorsalis pedis flap. The area of skin defect ranged from 5 cm x 4 cm to 7 cm x 6 cm. The area of flaps ranged from 6 cm x 5 cm to 8 cm x 7 cm. The donor site was repaired by the skin grafting. RESULTS: Arterial crisis occurred in 1 case after 1 day of one-stage operation, and was cured after vascular exploration, and the amputated fingers survived in the others. The reconstructed thumbs and flaps survived after two-stage operation, and the skin graft at donor site survived. The patients were followed up 1-4 years (mean, 2.8 years). The reconstructed thumbs had good appearance and satisfactory opposition and finger-to-finger functions. According to the standard functional evaluation issued by Hand Surgery Association of Chinese Medical Association, the scores of survival fingers were 73-91 (mean, 84); the results were excellent in 7 cases and good in 2 cases with an excellent and good rate of 100%. CONCLUSION: Temporary ectopic implantation of amputated finger to foot combined with dorsalis pedis flap can be used to reconstruct thumb and repair skin defect of the hand.

Soluble epoxide hydrolase: a promising therapeutic target for cardiovascular diseases.

Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP450) products of arachidonic acid and EETs are endogenous lipid mediators synthesized by the vascular endothelium which perform important biological functions, including vasodilation, anti-inflammation, antimigratory, and cellular signaling regulations. However, EETs are rapidly degraded by soluble epoxide hydrolase (sEH) to the corresponding diols: dihydroxyeicosatrienoic acids (DHETs), which have little active in causing vasorelaxation. A number of studies have supported that the inhibition of sEH (sEHIs) had cardiovascular protective effects in hypertension, cardiac hypertrophy, atherosclerosis, ischemia-reperfusion injury, and ischemic stroke. Moreover, sEHIs could slow the progression of inflammation, protect end-organ damage and prevent ischemic events, also, attenuate endothelial dysfunction, suggesting that the pharmacological blockade of sEH might provide a broad and novel avenue for the treatment of many cardiovascular diseases.

Involvement of profilin-1 in angiotensin II-induced vascular smooth muscle cell proliferation.

Profilin-1, a regulator of actin polymerization, has recently been linked to vascular hypertrophy and remodeling. Whether profilin-1 is involved in angiotensin (Ang) II-induced proliferation of vascular smooth muscle cells leading to vascular remodeling in hypertension remains unclear. The present study was designed to analyze the correlation of profilin-1 and vascular remodeling during hypertension and to evaluate the role of profilin-1 in proliferation of vascular smooth muscle cells and the underlying mechanisms. The vascular morphology and the expression of profilin-1 in arterial tissues of spontaneously hypertensive rats and Wistar-Kyoto rats were assessed. The profilin-1 expression was significantly increased concomitantly with definite vascular remodeling by evaluating the media thickness, lumen diameter, media thickness-to-lumen diameter ratio and mean nuclear area in artery media in spontaneously hypertensive rats, which was inhibited by treatment with losartan. In cultured rat aortic smooth muscle cells (RASMCs), Ang II induced profilin-1 expression in a dose- and time-dependent manner. Knockdown of profilin-1 using small hairpin RNA inhibited Ang II-induced proliferation of RASMCs. Moreover, blockade of JAK2/STAT3 signaling pathway also inhibited Ang II-induced proliferation of RASMCs and profilin-1 expression. These results suggest that profilin-1 mediates the proliferation of RASMCs induced by Ang II via activation of Ang II type 1 receptor/JAK2/STAT3 signaling pathway, which may contribute to vascular remodeling in hypertension.

Destruction of inorganic municipal solid waste incinerator fly ash in a DC arc plasma furnace.

Due to the toxicity of dioxins, furans and heavy metals, there is a growing environmental concern on municipal solid waste incinerator (MSWI) fly ash in China. The purpose of this study is directed towards the volume-reduction of fly ash without any additive by thermal plasma and recycling of vitrified slag. This process uses extremely high-temperature in an oxygen-starved environment to completely decompose complex waste into very simple molecules. For developing the proper plasma processes to treat MSWI fly ash, a new crucible-type plasma furnace was built. The melting process metamorphosed fly ash to granulated slag that was less than 1/3 of the volume of the fly ash, and about 64% of the weight of the fly ash. The safety of the vitrified slag was tested. The properties of the slag were affected by the differences in the cooling methods. Water-cooled and composite-cooled slag showed more excellent resistance against the leaching of heavy metals and can be utilized as building material without toxicity problems.

Salvage of amputated thumbs by temporary ectopic implantation.

PURPOSE: To determine the indications and benefits of ectopic implantation in the salvage of amputated thumb. BASIC PROCEDURES: Two cases of avulsed amputated thumbs were temporarily ectopically implanted onto the forearm and foot, with microvascular anastomoses. When the stump condition allowed, and the soft-tissue defects were repaired, the ectopic implanted thumbs were replanted to their anatomic positions. RESULTS: Both thumbs survived the temporary ectopic implantation and second-stage replantation. The length of the thumbs was maintained, and the thumbs regained their function in 16- and 10-week follow-ups. CONCLUSIONS: Temporary ectopic implantation of amputated parts provides an innovative procedure for the salvage of amputated thumbs under special circumstances. Although this procedure is very demanding, it does deserve special consideration in reconstructive microsurgery, since it offers the possibility to salvage amputated thumbs with extensive soft tissue loss of the hand, by preserving the anatomy and restoring the function of severely injured hands.