These results suggest that the anti-inflammatory properties of nano-Pt may be attributed to their downregulation of the NFκB signaling pathway in macrophages, thus supporting the use of nano-Pt as an anti-inflammatory agent.

Intra-cellular reactive nitrogen/oxygen species and apoptosis play important roles in ultraviolet (UV)-induced inflammatory responses in the skin. Astaxanthin (AST), a xanthophyll carotenoid, exhibits diverse clinical benefits. The protective effects of AST against UV-induced apoptosis were investigated in the present study. Astaxanthin (5 μm) caused a significant decrease in the protein content and the mRNA levels of inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2, and decreased the release of prostaglandin E2 from HaCaT keratinocytes after UVB (20 mJ/cm(2) ) or UVC (5 mJ/cm(2) ) irradiation. No significant protective effects against UV-induced reactive oxygen species (ROS) were observed in AST-pretreated cells. Astaxanthin caused a significant inhibition of UV-irradiation-induced apoptosis, as evidence by a DNA fragmentation assay. Furthermore, we found that the treatment with AST caused a reduction in the UVB- or UVC-induced protein and mRNA expression of macrophage migration inhibitory factor (MIF), IL-1β and TNF-α in HaCaT keratinocytes. These results suggest that AST effectively protects against UV-induced inflammation by decreasing iNOS and COX-2, and thereby inhibiting the apoptosis of keratinocytes.

Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O2• −) and hydroxyl radical (•OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.

Plasma is generated by ionizing gas molecules. Helium (He)-based cold atmospheric plasma (CAP) was generated using a high-voltage power supply with low-frequency excitation (60 Hz at 7 kV) and He flow at 2 l/min. Platinum nanoparticles (Pt-NPs) are potent antioxidants due to their unique ability to scavenge superoxides and peroxides. These features make them useful for the protection against oxidative stress-associated pathologies. Here, the effects of Pt-NPs on He-CAP-induced apoptosis and the underlying mechanism were examined in human lymphoma U937 cells. Apoptosis was measured after cells were exposed to He-CAP in the presence or absence of Pt-NPs. The effects of combined treatment were determined by observing the changes in intracellular reactive oxygen species (ROS) and both mitochondrial and Fas dependent pathway. The results indicate that Pt-NPs substantially scavenge He-CAP-induced superoxides and peroxides and inhibit all the pathways involved in apoptosis execution. This might be because of the SOD/catalase mimetic effects of Pt-NPs. These results showed that the Pt-NPs can induce He-CAP desensitization in human lymphoma U937 cells.

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Since polyacrylic acid capped platinum nano-particles (nano-Pts) are known to have a unique ability to quench superoxide (O2(-)) and hydrogen peroxide (H2O2), the anti-oxidant activity of nano-Pts against apoptosis induced by x-irradiation in human lymphoma U937 cells was investigated. DNA fragmentation assay, Annexin V-FITC/PI by flow cytometry and Giemsa staining revealed a significant decrease in apoptosis induced by 10 Gy, when cells were pre-treated with nano-Pts in a dose-dependent manner. Pre-treatment with nano-Pts significantly decreased radiation-induced reactive oxygen species (ROS) production, Fas expression and loss of mitochondrial membrane potential as determined by flow-cytometry. Furthermore, western blot analysis also showed that the expression of cleaved caspase-3, Bid and cytosolic cytochrome-c were significantly reduced in nano-Pts pretreated cells. Due to the catalase mimetic activity of nano-Pts, these results indicate that pre-treatment of U937 cells with nano-Pts significantly protect radiation-induced apoptosis by inhibiting intracellular ROS (mainly H2O2), which plays a key role in the induction of apoptosis, because of no practical observation of intracellular O2(-) formation.

IntroductionLiving tissue is complexly heterogenic. The processes are mostly chemical reactions, where energy absorption-emission is a central point. The energy liberated by metabolic activity appears in the bodytemperature, which is also very heterogenic by its sources, but is averaged by natural heat-conduction and the connected temperature equalisation. Hyperthermia is a thermal process, defined by a temperature-elevation in the target [1]. The mass-or volume-specific energy absorption (defined by the specific absorption rate [SAR]) increases the temperature.In the definition of hyperthermia, temperature is the obligatory parameter, used for dosing by considering the time for which it was effective [2]. Consequently, the treatment has to be identified by temperature, or at least by the specific energy absorption rate (SAR) in the target. The temperature and the energy-deposition must therefore be controlled.Electromagnetic energy delivery could be by four not completely independent categories, depending on the coupling of the fields to the object; it could be radiation, inductive, capacitive or galvanic coupling [3,4]. All of the interactions have variability in their absorption processes [5], in addition to the structural variations. Consequently, the SAR has microscopic medley values in the living target.Temperature is the average energy of the particles involved in the absorption process. This general temperature is composed of the various different microscopic heating areas, which could be equalised by the heat-conduction and convection in their surroundings by various timecharacters. The macroscopic temperature is a gross-average of all of the microscopic temperatures and their spread-processes.There are some very high-temperatures (over the protein denaturation [6] that can be locally concentrated and are relatively short time applications. It is limited to a very small volume by various interstitial methods, including the most popular radiofrequency (RF) ablation techniques. However, most of the hyperthermia practices in oncology are locally or regionally devoted to solving hyperthermia effects in shallow and deep-seated tumours [4]. The problems in these methods are simply connected to the focusing of heat-energy. The energy can be focused by choosing the targeted volume, but due to the non-invasive solutions, the input power is limited by adverse effects, so longer duration is necessary to heat up the target. The longer heating time completely changes the situation; we have to take into account the natural movements of the patient, which heats up the healthy environment, and naturally occurs because of the effective heat-diffusion and heat-conduction in the body. The energy can be focused for longer times to a chosen target volume, but the heat (and the temperature) is not focusable for longer, as it naturally spreads.The consequences of heat spreading can dramatically change the complete hyperthermia process. The homeostatic regulation of the body tries to re-establish the homeostatic equilibrium. C...

Shikonin (SHK), a natural naphthoquinone derived from the Chinese medical herb Lithospermum erythrorhizon, induces both apoptosis and necroptosis in several cancer cell lines. However, the detailed molecular mechanisms involved in the initiation of cell death are still unclear. In the present study, caspase-dependent apoptosis was induced by SHK treatment at 1μM after 6h in U937 cells, with increase in DNA fragmentation, generation of intracellular reactive oxygen species (ROS), fraction of cells with low mitochondrial membrane potential (MMP), and in the expression of BH3 only proteins Noxa and tBid. Interestingly, caspase-independent cell death was also detected with SHK treatment at 10μM, observed as increase in SYTOX® Green staining and release of lactate dehydrogenase (LDH). Necrostatin-1 (Nec-1) completely inhibited the SHK-induced leakage of LDH and SYTOX® Green staining. Cell permeable exogenous glutathione (GSH) completely inhibited 1μM SHK-induced apoptosis and converted 10μM SHK-induced necroptosis to apoptosis. Gene expression profiling revealed that 353 genes were found to be significantly regulated by 1μM and 85 genes by 10μM of SHK treatment, respectively. Among these genes, the transcription factor 3 (ATF3) and DNA-damage-inducible transcript 3 (DDIT3) were highly expressed at 1μM of SHK treatment, while tumor necrosis factor (TNF) expression mainly increased at 10μM treatment. These findings provide novel information for the molecular mechanism of SHK-induced apoptosis and necroptosis.