Hybrid Sono-Photodynamic Combination Therapy Mediated by Water-Soluble Gallium Phthalocyanine Enhances the Cytotoxic Effect against Breast Cancer Cell Lines.

Breast cancer is a life-threatening disease that is gaining increasing importance due to its rising incidence, highlighting the need for novel treatment methods with the least disadvantages. Recently, scientists have focused on developing therapeutic treatment modalities for effective cancer treatment. In contrast to conventional cancer treatment methods such as immunotherapy, surgery, chemotherapy, or radiotherapy, photodynamic therapy (PDT) is gaining prominence. Besides, sonodynamic treatment (SDT) is a noninvasive therapeutic approach that uses ultrasound to induce high tissue penetration. In both methods, sensitizers are activated to generate cytotoxic reactive oxygen species such as •OH and 1O2. In particular, the combined use of hybrid and complementary treatment methods has become an important modality in cancer treatment in recent years. Sono-photodynamic therapy (SPDT), which is an important method applied in combination with PDT and SDT, has started to be preferred in terms of reducing potential side effects compared to monotherapy. One of the most important types of sensitizers used in PDT and SDT is known as phthalocyanines (Pcs). Motivated by these facts, this research presents the sono-photochemical, in vitro cytotoxicity, and theoretical evaluation of water-soluble gallium phthalocyanine (GaPc). The results indicate that the quantum yield of the generation of singlet oxygen increased in sono-photochemical studies (ΦΔ = 0.94), compared to photochemical studies (ΦΔ = 0.72). In vitro analyses revealed that GaPc did not exhibit significant cytotoxic effects at the specified varying concentration doses (1-20 µM). Furthermore, GaPc-mediated SPDT triggered cell death by inducing reactive oxygen species formation in the breast cancer cell line (MCF-7). The interaction mechanism of the GaPc with EGFR and VEGFR2 target proteins, which are critical regulators of metastasis, proliferation, and angiogenesis, was investigated by molecular docking simulation. GaPc has effective binding affinities against target proteins, and this affinity was found to be the highest against VEGFR2. Molecular docking results showed a good correlation with the obtained biological results. Eventually, this molecular building of the efficient water-soluble phthalocyanine-based sensitizer is a potential therapeutic for PDT, SDT, and SPDT applications.

Disposable nanosensor for the electrochemical determination of the interaction between DNA, and a mycotoxin, patulin.

Silicon dioxide nanoparticles were synthesized and disposable screen-printed electrodes were modified with these nanoparticles to electrochemically detect the interaction between DNA and patulin, a mycotoxin. Firstly, the synthesized silicon dioxide nanoparticles were chemically characterized by X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FT-IR). Microscopic characterization of the nanoparticles was performed by Transmission Electron Microscopy (TEM) and Energy-dispersive X-ray spectroscopy (EDX). The surface of the silicon dioxide nanoparticle-modified screen-printed electrode was characterized by Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). SiNP modification resulted in a 2-fold increase in surface area and a 2.3-fold enhancement in the signal. The detection limit (LOD) for the electrochemical patulin determination was calculated as 1.15 µg/mL, and the linear concentration range was found to be 3.2-20 µg/mL. The mode of interaction between patulin and dsDNA was determined through a molecular docking study. After the interaction between patulin and dsDNA, approximately 86 % and 23 % decreases were observed in patulin and guanine oxidation signals, respectively. The S % value for patulin was calculated by utilizing the decrease in the guanine signal after the interaction.

Nonlinear analysis of electrodermal activity signals for healthy subjects and patients with chronic obstructive pulmonary disease.

It is known that signals recorded from physiological systems represent nonlinear features. Several recent studies report that quantitative information about signal complexity is obtained by using nonlinear analysis algorithms. Chronic obstructive pulmonary disease (COPD) is one of the causes of mortality worldwide with an increasing prevalence. This study aims to investigate nonlinear parameters such as largest Lyapunov exponent (LLE) and correlation dimension of electrodermal activity signals recorded from healthy subjects and patients with COPD. Electrodermal activity signals recorded from 14 healthy subjects and 24 patients with COPD were analysed. Auditory and tactile stimuli were applied at different time intervals during the recording process. Signals were reconstructed in the phase space compatible with theory and LLE and correlation dimension values were calculated. Statistical analysis was performed by using Shapiro-Wilk normality test, one-way analysis of variance (ANOVA) with Bonferroni post-test and Kruskal-Wallis non-parametric test. It was determined that the chaoticity and the complexity of the system increased in the presence of COPD. The systematic auditory stimuli increases chaoticity more than random auditory stimuli. Furthermore it was observed that participants develop habituation to the same auditory stimuli in time. There is no significant difference between COPD groups. Different results were found for the tactile stimuli applied to right or left ear. The results revealed that the nonlinear analysis of physiological data can be used for the development of new strategies for the diagnosis of chronic diseases.

Effect of pulsed electromagnetic field on MMP-9 and TIMP-1 levels in chondrosarcoma cells stimulated with IL-1ß.

Chondrosarcoma, the second most common type of bone malignancy, is characterized by distant metastasis and local invasion. Previous studies have shown that treatment by pulsed electromagnetic field (PEMF) has beneficial effects on various cancer cells. In this study, we investigated the effects of PEMF applied for 3 and 7 days on the matrix metalloproteinase (MMP) levels in chondrosarcoma SW1353 cells stimulated with two different doses of IL-1ß. SW1353 cells were treated with (0.5 and 5 ng/ml) IL-1ß and PEMF exposure was applied either 3 or 7 days. MMP-9 and TIMP-1 levels were measured in conditioned media by enzyme-linked immunosorbent assay. The results were relative to protein levels. Statistical analyses were performed using one-way analysis of variance (ANOVA). P<0.05 was considered significant. PEMF treatment significantly decreased MMP-9 protein levels in human chondrosarcoma cells stimulated with 0.5 ng/ml IL-1ß at day 7, whereas it did not show any effect on cells stimulated with 5 ng/ml IL-1ß. There was no significant change in TIMP-1 protein levels either by IL-1ß stimulation or by PEMF treatment. The results of this study showed that PEMF treatment suppressed IL-1ß-mediated upregulation of MMP-9 protein levels in a dual effect manner. This finding may offer new perspectives in the therapy of bone cancer.