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.

Evaluation of combined effects of brief electrical stimulation and Schwann-like cells on sciatic nerve injury model.

Severe nerve injuries can be treated with electrical stimulation and stem cell therapies, but little is known about the potential benefits of combining these two treatments. In an effort to investigate this combination, we conducted a study to evaluate the effectiveness of electrical stimulation and Schwann-like cell transplantation in female Wistar albino rats. Our study consisted of five groups of rats: a sham group, an injury group, an electrical stimulation group, a Schwann-like cell group, and a combination group. The experimental groups received electrical stimulation, Schwann-like cell transplantation, or both. The animals sciatic function index was evaluated during a 6-week recovery period, and nerve conduction velocity, wet muscle mass, and nerve tissues were also analyzed. The results of the study showed that all experimental groups had a faster functional recovery compared to the injury group, although the difference between groups was not statistically significant. Both the combination group and the Schwann-like cell transplantation group had a higher nerve conduction velocity compared to the other experimental groups. However, there was no significant difference between the combination and Schwann-like cell transplantation groups. Nonetheless, histological analysis showed a better axonal reorganization in the combination group. The study provides preliminary evidence of the potential benefits of combining electrical stimulation and Schwann-like cell transplantation in treating severe nerve injuries. However, further studies with larger sample sizes are needed to confirm these findings and optimize the treatment parameters.

The synthesis of novel water-soluble zinc (II) phthalocyanine based photosensitizers and exploring of photodynamic therapy activities on the PC3 cancer cell line.

In this study, Schiff base substituted phthalocyanine complexes (Zn1c, Zn2c) and their quaternized derivatives (Q-Zn1c, Q-Zn2c) were synthesized for the first time. Their structures have been characterized by FT-IR, 1H-NMR, UV-Vis, mass spectrometry and elemental analysis as well as. The photophysicochemical properties (fluorescence, singlet oxygen and photodegradation quantum yield) of these novel complexes were investigated in dimethylsulfoxide (DMSO) for both non-ionic and quaternized cationic phthalocyanine complexes and in aqueous solution for quaternized cationic phthalocyanine complexes. Water soluble cationic phthalocyanine compounds gave good singlet oxygen quantum yield (0.65 for Q-Zn1c, 0.66 for Q-Zn2c in DMSO; 0.65 for Q-Zn2c in aqueous solution). The binding of Q-Zn1c and Q-Zn2c to BSA/DNA was studied by using UV-Vis and fluorescence spectroscopy and these. Studies indicate that the mechanism of BSA quenching by quaternized zinc(II) phthalocyanines was static quenching. Quaternized zinc(II) phthalocyanines interacted with ct-DNA by intercalation. Quaternized zinc(II) phthalocyanines caused a decrease in cell viability and triggered apoptotic cell death after PDT was applied at a concentration that did not have a toxic effect on their own. Q-Zn1c and Q-Zn2c mediated PDT reduced the activity of SOD, CAT, GSH while increased MDA level in the prostate cancer cells. Furthermore, expression of apoptotic proteins after PDT was examined. The results revealed that the synthesized water soluble quaternized zinc(II) phthalocyanine complexes (Q-Zn1c and Q-Zn2c) are promising potential photosensitizers for PDT.

Sensory­motor performance and neurochemical effects in the cerebral cortex of brain­derived neurotrophic factor heterozygous mice fed a high­cholesterol diet.

Reports suggest that a high­cholesterol diet may induce neuroinflammation, oxidative stress, and neurodegeneration in brain tissue. Brain­derived neurotrophic factor (BDNF) might play a role in protecting against changes induced by high cholesterol. We aimed to assess behavioral correlates and biochemical alterations in the motor and sensory cortices following a high­cholesterol diet under normal and reduced BDNF concentrations. C57Bl/6 strain, wild­type (WT) and BDNF heterozygous (+/­) mice were used to reveal the effects of endogenous BDNF concentrations. We compared diet and genotype effects using four experimental groups: WT and BDNF heterozygous (+/­) groups of mice were each fed a normal or high­cholesterol diet for 16 weeks. The cylinder test and wire hanging test were performed to evaluate neuromuscular deficits and cortical sensory­motor functions, respectively. In addition, neuroinflammation was assessed by tumor necrosis factor alpha and interleukin 6 levels measured in the somatosensory and motor areas. Additionally, MDA levels and SOD and CAT activity were evaluated as oxidative stress parameters. Results showed that a high­cholesterol diet significantly impaired behavioral performance in the BDNF (+/­) group. Diet did not change the levels of neuroinflammatory markers in any of the groups. However, MDA levels, an indicator of lipid peroxidation, were significantly higher in the high­cholesterol­fed BDNF (+/­) mice. The results suggest that BDNF levels might be a critical factor in determining the extent of neuronal damage induced in the neocortex by a high­cholesterol diet.

Comparison of sonodynamic, photodynamic and sonophotodynamic therapy activity of fluorinated pyridine substituted silicon phthalocyanines on PC3 prostate cancer cell line.

BACKGROUND: Sonophotodynamic therapy (SPDT), a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT), may offer theraputic advantage. The therapeutic effects of sonodynamic, photodynamic, and sonophotodynamic of 5-(trifluoromethyl)-2-thiopyridine substituted silicon phthalocyanine (gy3) and its quaternized derivative (gy3q) were examined in vitro on prostate cancer using PC3 cells. METHODS: The SDT, PDT and SPDT efficiency was determined by using MTT test.Apoptosis mechanism was evaluated by HOPI staining. RESULTS AND DISCUSSIONS: According to MTT results, the phthalocyanines decreased cell viability when compared with a control group. Also, apoptosis measurement data represents that the phthalocyanines would produce much better therapeutic outcomes compare to PDT and SDT by utilizing SPDT. Further studies should be performed to understand the effectiveness of SPDT.

Investigation of effects of quercetin and low-level laser therapy in cisplatin-induced in vitro peripheral neuropathy model.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-dependent side effects of cisplatin. The loss of sensory neurons is observed in CIPN. There are many methods to minimalize CIPN symptoms such as pharmacological agents and photobiostimulation but the mechanisms of these methods are unclear. Our study is aimed at determining the effects of quercetin and low-level laser therapy (LLLT) in undifferentiated and nerve growth factor-differentiated PC12 cells in cisplatin-induced peripheral neuropathy. PC12 cells with cisplatin were co-treated with quercetin and LLLT (diode pumped all-solid-state laser, 670 nm, output 500 mW, and the laser beam surface area was 1.96 cm2). The effects of quercetin and LLLT on GAP-43 and Synapsin I expressions were analyzed by real-time PCR, cell viability was assessed by MTT assay, Annexin and dead assay measured the induction of apoptosis, the alterations in mitopotential were assessed by mitopotential assay, and lactate dehydrogenase activity in cells was analyzed. All experiment data were analyzed by the Tukey test and applied as a post hoc test, and statistical evaluation was made. Our results indicated that cisplatin increased apoptosis (24,210 ± 2189, 46,504 ± 8246) cells, mitochondrial dysfunction (44,312 ± 0.751, 68,788 ± 1271), and LDH activity (62,821 ± 8245, 87,838 ± 8116). Furthermore, it decreased cell viability (42,447 ± 1780, 36,140 ± 3682) and inhibited GAP-43 and Synapsin I genes in undifferentiated and differentiated PC12 cells. However, apoptosis, the alterations in mitopotential, and lactate dehydrogenase activity decreased by applications of quercetin and LLLT. It has been recommended that quercetin and low-level laser therapy roles on cisplatin-induced peripheral neuropathy should be investigated in vivo, and the relationship between quercetin and low-level laser therapy should be molecular.

Ultrasound versus Light: Exploring Photophysicochemical and Sonochemical Properties of Phthalocyanine-Based Therapeutics, Theoretical Study, and In Vitro Evaluations.

Photodynamic therapy (PDT) applications carried out with the assistance of ultrasound have attracted significant attention in recent years. The use of phthalocyanines, which are an important component as photosensitizers in PDT, is becoming more important day by day. In therapeutic applications, phthalocyanines can promote the production of reactive oxygen species. Motivated by this fact, the syntheses of metal-free (2), gallium (3), and indium (4) phthalocyanines have been achieved by substituting 4-(cinnamyloxy)phthalonitrile for the first time to evaluate their therapeutic applications. Additionally, photophysicochemical, sonophotochemical, and in vitro evaluations of phthalocyanines have been reported. To the best of our knowledge, this is the first study of the use of phthalocyanines with different metal ions as potential photosensitizers for sonophotodynamic therapy (SPDT) applications in gastric cancer cell lines. The results show that the quantum yield of the generation of singlet oxygen increased in sonophotochemical studies (ΦΔ = 0.55 (2), 0.85 (3), 0.96 (4)), compared to photochemical studies (ΦΔ = 0.22 (2), 0.61 (3), 0.78 (4)). The density functional theory (DFT) results are in good agreement with the experimental results and suggest increased reactivity of phthalocyanines 3 and 4 in various redox processes, thus implying their applicability and usefulness as potential therapeutic agents. These phthalocyanines are effective sensitizers for PDT, sonodynamic therapy (SDT), and SPDT against MKN-28 gastric cancer cell line in vitro. All three treatments decreased cell viability and induced apoptosis in the gastric cancer cell line. However, indium phthalocyanine (4)-mediated SPDT was a more effective treatment modality compared to indium phthalocyanine (4)-mediated PDT and SDT. Also, indium phthalocyanine (4) was found to be a more effective sensitizer to activate apoptosis compared to the other phthalocyanines. To sum up, phthalocyanine-mediated SPDT enhances the cytotoxic effect on gastric cancer cells more than the effect of SDT or PDT alone.

Evaluation of photodynamic therapy against Leishmania tropica promastigotes using different photosensitizers.

BACKGROUND: Photodynamic therapy is a two-step procedure, involving the use of photosensitizing agents followed by selective illumination of the target lesion with visible light. Photodynamic therapy has been described recently as a promising strategy for treatment of leishmaniasis. This study aims to evaluate the in vitro phototoxic, morphological, and apoptotic effect of methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy on the viability of Leishmania tropica promastigotes. METHODS: Parasites were treated with methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a or/and methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy, and cell proliferation, morphological changes, and apoptosis were evaluated by XTT, giemsa staining, DAPI staining, and DNA fragmentation, respectively. RESULTS: Parasite viability was significantly different in between the groups treated with methylene blue, toluidine blue, and pheophorbide a, with or without irradiation. chloro-aluminum phthalocyanine treatment did not lead to any alterations in cell viability in Leishmania tropica promastigotes with or without irradiation. DAPI staining results indicated that apoptotic bodies and nucleus fragmentation started to be visible in methylene blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy groups. DNA ladder pattern which is used to define apoptosis was observed in irradiated methylene blue, chloro-aluminum phthalocyanine, and pheophorbide a groups. CONCLUSIONS: The results revealed that apoptosis-induced cell death was observed in Leishmania tropica promastigotes after the application of photosensitizers in combination with light irradiation.

Novel approaches for COVID-19 diagnosis and treatment: a nonsystematic review.

Since COVID-19 pandemic has been continuously rising and spreading, several original contributions and review articles on COVID-19 started to appear in the literature. The review articles are mainly focus on the current status of the pandemic along with current status of the corona diagnosis and treatment process. Due to some disadvantages of the currently used methods, the improvement on the novel promising diagnosis and treatment methods of corona virus is very important issue. In this review, after briefly discussing the status of current diagnosis and treatment methods, we present to the scientific community, novel promising methods in the diagnosis and treatment of COVID-19. As with other novel approaches, first, the diagnosis potential of mass spectroscopy and optical spectroscopic methods such as UV/visible, infrared, and Raman spectroscopy coupled with chemometrics will be discussed for the corona virus infected samples based on the relevant literature. In vibrational spectroscopy studies, due to complexity of the data, multivariate analysis methods are also applied to data. The application of multivariate analysis tools that can be used to extract useful information from the data for diagnostic and characterisation purposes is also included in this review. The reviewed methods include hierarchical cluster analysis, principal component analysis, linear and quadratic discriminant analysis, support vector machine algorithm, and one form of neural networks namely deep learning method. Second, novel treatment methods such as photodynamic therapy and the use of nanoparticles in the in-corona virus therapy will be discussed. Finally, the advantages of novel promising diagnosis and treatment methods in COVID-19, over standard methods will be discussed. One of the main aims of this paper is to encourage the scientific community to explore the potential of this novel tools for their use in corona virus characterization, diagnosis, and treatment.

Titaniumdioxide mediated sonophotodynamic therapy against prostate cancer.

In this study, we aimed to investigate of antitumor efficiency of titanium dioxide mediated photodynamic (PDT), sonodynamic (SDT), and sonophotodynamic (SPDT) therapies with a possible mechanism against the PC3 prostate cancer cell line. SPDT is a new approach to cancer treatment that combines sonodynamic and photodynamic therapies. On the other hand, Titanium dioxide (TiO2) has been used in many applications in pharmaceutical products and cosmetics, industrial products, and medicines. TiO2 nanoparticles will be useful for the treatment of cancer with PDT and SDT as the sensitizers in medicine. In this study, TiO2 nanoparticles were used for an in vitro comparison between the PDT, SDT, SPDT damages on prostate cancer cell lines. For this purpose, the cells were incubated in RPMI-1640 media with various concentrations of TiO2 and subjected to 0,5 W/cm2 ultrasound and/or 0,5 mJ/cm2 light irradiation. The prostate cancer cells were irradiated with light and exposed with the US and both for SPDT in the presence and/or absence of TiO2. Cell viability was measured using by MTT test after treatments. Investigate to apoptosis mechanism, Propidium iodide and Hoechst 33342 staining were used and the results showed that apoptotic cell bodies were increased compared with other groups. According to western blot analyses, caspase-3, caspase-8, PARP, and Bax levels were decreased after treatments, whereas the expression levels of caspase-9 were increased. Biochemical results showed that after treatments MDA levels were increased while SOD, CAT, GSH levels were decreased. In conclusion, TiO2-mediated SPDT may provide a promising approach for prostate cancer therapy and might play a key role in the apoptotic mechanism of these treatments.

Comparison of the Effects of Electroacupuncture and Melatonin on Nerve Regeneration in Experimentally Nerve-Damaged Rats.

Background: Development of methods to accelerate nerve regeneration in peripheral nerve damage is important. Electroacupuncture is a new therapeutic method that combines traditional acupuncture with modern electrotherapy. Melatonin has been shown to reduce nerve damage. Objectives: In this study, we aimed to determine and compare the therapeutic effects of electroacupuncture and melatonin on rat sciatic nerve injury. Methods: A total of 56 adult male Wistar Albino rats were divided into four study groups with 14 animals in each group: intact control (group I), subcutaneous saline (group II), subcutaneous melatonin (group III), and electroacupuncture (group IV). Surgical procedure including unilateral (right) sciatic nerve injury was applied to groups II, III, and IV. Saline and melatonin started immediately after surgery for six weeks, while electroacupuncture was given two weeks after surgery for 3 weeks. Functional and histological assessments were used as outcome measurements. Results: Sciatic nerve damage caused a significant decrease in nerve conduction velocity. Both electroacupuncture treatment and melatonin treatment significantly increased the nerve conduction velocity. Both sciatic functional recovery and histological regeneration were faster in these treatment groups compared to the saline. However, no significant difference was observed between the two treatment groups. Conclusion: Electroacupuncture and melatonin are promising alternative treatment strategies for peripheral nerve damage and can be examined in detail in future studies.

Pheophorbide a-mediated sonodynamic, photodynamic and sonophotodynamic therapies against prostate cancer.

Anticancer efficiencies and mechanisms of Pheophorbide-a-mediated photodynamic, sonodynamic and sonophotodynamic therapies were investigated in vitro using androgen-sensitive (LNCaP) and androgen insensitive (PC3) prostate cancer cell lines. The cells were incubated in RPMI-1640 media at various concentrations of Pheophorbide-a. The media was treated with 0.5 W/cm2 ultrasound and/or 0.5 mJ/cm2 light irradiation. Cell proliferation in both cell lines was inhibited most effectively by sonophotodynamic therapy in comparison to that of both monotherapies. LNCaP cells were more sensitive to the applied treatments and the cell survival in LNCaP cell line was observed to be less than that of PC3 cell line. The results of histochemical analysis showed that there were more apoptotic cells in the treatment groups in comparison to control group. Additionally, the treatments induced apoptosis deduced by the overexpressed levels of caspase-3, caspase-8, PARP, and Bax proteins, while the expression levels of caspase-9 and Bcl-2 proteins were observed to be lower than those of control group. Treatments led to an increase in the oxidative stress markers, ROS and MDA, but a decrease in the activities of antioxidant enzymes, SOD, CAT and GSH. The results of this study revealed that Pheophorbide a-mediated sonophotodynamic therapy more efficiently activates the apoptotic mechanisms in prostate cancer cells and thus may provide a promising approach for treatment.

Pterostilbene administration improves the recovery potential of extremely low-frequency magnetic field in acute renal ischemia-reperfusion injury: an FTIR spectroscopic study.

Renal ischemia-reperfusion (I/R) injury, one of the drastic outcomes of renal failure and organ transplantation, tends to deteriorate over time; therefore, noninvasive therapeutic strategies will avail the progression-free survival of the patients. Magnetic field has been proposed as a noninvasive treatment strategy; however, with recent scientific advances, many controversies have arisen regarding its efficacy. Pterostilbene, a natural analog of resveratrol, was documented to be effective in treatment of I/R injuries. This study aims to assess the acute therapeutic effects of combined extremely low-frequency magnetic field (ELF-MF) and pterostilbene treatment on renal I/R injury. After induction of renal I/R in Wistar rats, treatments of 50 Hz, 1 mT ELF-MF applied alone or in combination with pterostilbene were applied for 5 consecutive days. Kidney homogenates were analyzed by Fourier transform infrared spectroscopy. I/R injury resulted in an altered protein and lipid structure with the dominance of longer acyl chains; a slight decrease in lipid, protein, unsaturated lipid, and unsaturated/saturated lipid content; and an increase in membrane fluidity and lipid peroxidation in rat kidneys. Although ELF-MF treatment alone was not sufficient to restore all ischemia-induced alterations, the combined treatment strategy of pterostilbene administration in the presence of ELF-MF was successful and warrants further investigation.

Mathematical morphology-based imaging of gastrointestinal cancer cell motility and 5-aminolevulinic acid-induced fluorescence.

The aim of this study was the quantitative evaluation of gastrointestinal cancer cell motility and 5-aminolevulinic acid (5-ALA)-induced fluorescence in vitro using mathematical morphology and structural analysis methods. The results of our study showed that MKN28 cells derived from the lymph node have the highest motility compared with AGS or HCT116 cells derived from primary tumors. Regions of single cells were characterized as most moving, and "tightly packed" cell colonies as nearly immobile. We determined the reduction of cell motility in late passage compared to early passage. Application of 5-ALA caused fluorescence in all investigated cells, and the fluorescence was different with regard to the cell type and application time. We observed higher fluorescence in MKN28 cells. Comprehensive image analysis did not reveal any statistically significant difference in fluorescence intensity between "tightly packed" cell regions, where nearly no motility was registered and loosely distributed cells, where the highest cell motility was registered. In conclusions, our study revealed that MKN28 cells derived from the lymph node have higher motility and 5-ALA-induced fluorescence than AGS or HCT116 derived from primary tumors. Moreover, image analysis based on a large amount of processed data is an important tool to study these tumor cell properties.

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.

Early Alterations in Bone Characteristics of Type I Diabetic Rat Femur: A Fourier Transform Infrared (FT-IR) Imaging Study.

Alterations in microstructure and mineral features can affect the mechanical and chemical properties of bones and their capacity to resist mechanical forces. Controversial results on diabetic bone mineral content have been reported and little is known about the structural alterations in collagen, maturation of apatite crystals, and carbonate content in diabetic bone. This current study is the first to report the mineral and organic properties of cortical, trabecular, and growth plate regions of diabetic rat femurs using Fourier transform infrared (FT-IR) microspectroscopy and the Vickers microhardness test. Femurs of type I diabetic rats were embedded into polymethylmethacrylate blocks, which were used for FT-IR imaging and microhardness studies. A lower mineral content and microhardness, a higher carbonate content especially labile type carbonate content, and an increase in size and maturation of hydroxyapatite crystals were observed in diabetic femurs, which indicate that diabetes has detrimental effects on bone just like osteoporosis. There was a decrease in the level of collagen maturity in diabetic femurs, implying a decrease in bone collagen quality that may contribute to the decrease in tensile strength and bone fragility. Taken together, the findings revealed alterations in structure and composition of mineral and matrix components, and an altered quality and mechanical strength of rat femurs in an early stage of type I diabetes. The results contribute to the knowledge of structure-function relationship of mineral and matrix components in diabetic bone disorder and can further be used for diagnostic or therapeutic purposes.

Protoporphyrin IX-loaded magnetoliposomes as a potential drug delivery system for photodynamic therapy: Fabrication, characterization and in vitro study.

BACKGROUND: Protoporphyrin IX (PpIX) is a well-known photosensitizer that has great potential for use in photodynamic therapy (PDT). However, aggregation behavior of PpIX in neutral water makes it inappropriate for physiological studies. PpIX-loaded magnetoliposomes (MLs) were fabricated to increase PpIX biocompatibility. PpIX-loaded ML physical properties were characterized, and PpIX-loaded ML drug release behavior was investigated under the influence of an external magnetic field and heat. Toxicity and photodynamic effects of the complex were also examined using in vitro experiments with MCF-7 human breast cancer cells. METHODS: The magnetoliposomes were prepared with DPPC, DSPE-PEG2000 lipids and Fe3O4 nanoparticles. The toxicity and in vitro photodynamic effects of the PpIX-loaded MLs at various concentrations were studied using the MCF-7 cell line. RESULTS: The produced PpIX-loaded MLs exhibited an average hydrodynamic diameter of 221nm; however, TEM measurements indicated that the diameter of the PpIX-loaded MLs varied between 166 and 720nm. The iron content of the MLs affected cell viability less than the content of the iron free liposomes. Cell viability was reduced to 66% when the concentration of the PpIX-loaded MLs was 350nM, but when white light was applied for 5min, all of the cells that were exposed to concentrations of 250nM and higher PpIX died within 24h. CONCLUSION: The results of this study demonstrated the effective application of PpIX-loaded MLs for in vitro photodynamic therapy at nanomolar concentrations. The results also indicated that an LED light source provided sufficient energy to stimulate the PpIX molecules.

Assessment of the Effects of Extremely Low Frequency Electromagnetic Fields on Toxoplasma gondii.

BACKGROUND: The effects of extremely low frequency electromagnetic fields (ELF-EMF) on Toxoplasma gondii have not been explained yet. The aim of this study was to assess the possible effects of ELF-EMF on growth, survival time and viability of Toxoplasma gondii. In addition, the life span of Toxoplasma infected animals was investigated. METHODS: Sixty adult male BALB/c mice were used for in vivo and in vivo experiments in Laboratory of Biopyhsics and Parasitology of Medical Faculty, Adnan Menderes University, Turkey, in 2010. During in vivo experiments, pulsed and continuous EMFs were applied for 5 d to the infected mice. During in vivo experiments, pulsed and continuous EMF was applied to the tachyzoites within peritoneal exudates for 8 h/d at 4 °C and the tachyzoites were then injected to mice. In both experiments, the number of T. gondii in peritoneal exudates was counted and T. gondii protein bands patterns were investigated with polyacrylamide gel electrophoresis and Western Blotting. RESULTS: Pulsed and continuous EMF exposure reduced the number of T. gondii tachyzoites in comparison to controls. However, no statistically significant differences were observed at the patterns of protein bands among the samples. CONCLUSION: EMF exposure induces a decrease in the number of T. gondii. Further studies are required to understand the mechanism of EMF on intracellular parasites.

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.

Anthropometric methods in evaluation of chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is mainly expressed by weight loss with especially fat-free mass (FFM) depletion and a low body weight correlates with increased mortality and a poor prognosis. We investigated whether anthropometric body composition equations could be used for evaluation of the body composition in COPD. Thirty clinically stable patients with COPD and 13 healthy age matched control subjects underwent the skinfolds and circumference measurements in addition to body mass index (BMI) calculations. Body fat mass (BFM) and FFM were determined by using anthropometric equations. The percent BFM, predicted from body density either using Siri's or Brozek's equations was determined lower than that of calculated with equations by using BMI, age and gender. The values of BFM and body weight were reduced in patients with FEV1 < % predicted compared to other participants. The FFM values also dropped depending on the severity of COPD. BMI was not statistically different among the participants while FFM index (FFMI) reflected the nutritional status of the disorders. Anthropometric equations easily and cost effectively applied for prediction of % BFM, FFM, and FFMI in patients with COPD. In addition, the FFMI can be possibly used for expressing COPD severity.