Effects of thermal therapy combined with blue light-emitting diode irradiation on trimellitic anhydride-induced acute contact hypersensitivity mouse model.

BACKGROUD: The biological effect of phototherapy, which involves using visible light for disease treatment, has attracted recent attention, especially in dermatological practice. Light-emitting diode (LED) irradiation increases dermal collagen level and reduces inflammation. It has been suggested that thermal therapy and LED irradiation can modulate inflammatory processes. However, little is known about the molecular mechanism of the anti-inflammatory effects of thermal therapy and LED irradiation. OBJECTIVE: This study was to determine the anti-inflammatory effect of thermal therapy combined with LED irradiation on trimellitic anhydride (TMA)-induced acute contact hypersensitivity (CHS) mouse model. METHODS: Twenty-four BALB/c mice were randomly divided into the following groups: Vehicle group, TMA group, TMA + alternating thermal therapy group (Alternating group), and TMA + alternating + LED group (LED group). Ear swelling was measured based on the thickness of ear before and after each TMA challenge. Vascular permeability was evaluated by the extravasation of Evans blue dye. Serum IgE level, Th1/Th2/Th17 cytokines, and related transcription factors were measured using ELISA kits, and histological examination was illustrated in ear tissue. RESULTS: The LED group showed reduction in ear swelling response, vascular permeability, serum IgE levels, Th2/Th17 cytokine levels, and inflammatory cell infiltration. Moreover, the LED group showed increased Th1 cytokine levels. CONCLUSIONS: These results indicate that thermal therapy combined with LED irradiation alleviated TMA-induced acute CHS in the mouse model. Thermal therapy and phototherapy should be considered as a novel therapeutic tool for the treatment of skin inflammation.

Curcuminoids encapsulated liposome nanoparticles as a blue light emitting diode induced photodynamic therapeutic system for cancer treatment.

Unlike normal cells, cancer cells mutate to thrive in exaggerated levels of reactive oxygen species (ROS). This potentially makes them more susceptible to small molecule-induced oxidative stress. The intracellular ROS increase in cancer cells is a potential area under investigation for the development of cancer therapeutics targeting cancer cells. Visible photons of 430-490 nm wavelengths from a blue-light emitting diode (BLED) encompass the visible region of the spectrum known to induce ROS in cancer cells. Curcuminoids (CUR) naturally occurring photosensitizers sensitized by the blue wavelength of the visible light, well known for its potent anti-inflammatory and anticancer activity. Poor solubility and bioavailability, of the compound of the small molecule CUR restrict the therapeutic potential and limits CUR to be used as a photosensitizer. Here, our research group reports the use of small molecules CUR, encapsulated in liposome nanocarriers (LIP-CUR) coupled with blue light-emitting diode (BLED) induced photodynamic therapy (BLED-PDT). In A549 cancer cells in vitro, LIP-CUR coupled with BLED initiated BLED-PDT and triggered 1O2, ultimately resulting in caspase-3 activated apoptotic cell death. The combination of a non-cytotoxic dose of small molecule CUR co-treated with BLED to trigger BLED-PDT could be translated and be developed as a novel strategy for the treatment of cancer.

Radioiodine ablation in thyroid cancer patients: renal function and external radiation dose rate at discharge according to patient preparation.

BACKGROUND: An elevated thyroid stimulating hormone (TSH) level is essential for the uptake of radioiodine into thyroid remnants and residual thyroid cancer in patients undergoing high-dose radioiodine therapy (HD-RIT). Recently, the use of recombinant human thyroid stimulating hormone (rh-TSH) has increased in preference over the conventional method of thyroid hormone withdrawal (THW). However, the clinical influences of the two methods, aside from the therapeutic effects, have not been widely evaluated. The aim of this work was to investigate the influences of the two methods, particularly on the renal function and external radiation dose rate (EDR) from patients undergoing HD-RIT. METHODS: From February 2012 to November 2016, 667 patients (M:F=138:529, mean age: 47.7±11.8 years), who underwent first HD-RIT (120, 150, or 180 mCi, 1 mCi=37 MBq) for ablation of remnant thyroid tissue or residual thyroid cancer, were enrolled. Patients who were proven to have distant metastasis to lung or bone were excluded. Low- to high-risk patients based on 2015 American thyroid association management guidelines who underwent first HD-RIT in our department were included. The period from total thyroidectomy to HD-RIT was limited within 12 months. The following parameters were collected and evaluated: age, gender, histology type and TNM stage of thyroid cancer, glomerular filtration rate on the admission day for total thyroidectomy (baseline GFR), GFR on the day of HD-RIT (follow-up GFR), thyroglobulin (Tg) and TSH levels on the day of HD-RIT, and EDR on the discharge day after HD-RIT. RESULTS: There were 386 patients using the THW method and 281 patients choosing the rh-TSH method. The baseline GFR of the THW group (106±16 mL/min/1.73 m2) and that of the rh-TSH group (104±17 mL/min/1.73 m2) were within normal limits and there was no significant difference. However, follow-up GFR of the THW group (84±17 mL/min/1.73 m2) was much lower than that of the rh-TSH group (104±16 mL/min/1.73 m2) (P=0.000). In the THW group, the follow-up GFR decreased significantly (P=0.000), yet the follow-up GFR of the rh-TSH group was not statistically different when compared with its baseline GFR (P=0.142). EDRs were lower in all rh-TSH subgroups compared to those of THW subgroups with statistical significance. Tg and TSH levels were not different between the two groups, excluding a few small-sized subgroups analyses. CONCLUSIONS: In this retrospective analysis of renal function and EDR, the use of rh-TSH appears to help maintain renal function and finally decrease EDR in contrast to the THW method when undergoing HD-RIT.

Therapeutic application of light emitting diode: Photo-oncomic approach.

As a new light source, light emitting diode (LED) with high brightness and lower cost has been rapidly developed in medical application and light therapy. LED phototherapy can activate target cells with appropriate power and adequate energy density. This review provides general information on therapeutic applications of blue, green, yellow, red, and infrared LED in medical treatments for various physical abnormalities and on bio-imaging. The bio-imaging system is improved by decreasing the number of microscopes apparatuses including neutral-density filter, excitation filters and mechanical shutters. The numbers of excitation photons are increased and the fluorescent excitation efficiency is improved at cellular level. In the target tissue, the therapeutic effect of LEDs is dependent on incident photons irrespective of the system used to generate these photons. Photomodulated light from LED device is delivered in pulsed mode with specific pulse sequences and time. Too low or too high dose of energy may be ineffective at all. Clinical applications of LED light depending on different wavelengths are summarized. The author's photo-oncomic experiments using a specific blue light emitting diode were introduced, showing that blue LED possessed anti-proliferative and anti-metastatic abilities in cancer cells and mice. As a promising light source, photo-oncomic approach of blue LED could be applied to treat cancers and inflammatory diseases.

Inhibitory effect of blue light emitting diode on migration and invasion of cancer cells.

The aim of this study was to determine the effects and molecular mechanism of blue light emitting diode (LED) in tumor cells. A migration and invasion assay for the metastatic behavior of mouse colon cancer CT-26 and human fibrosarcoma HT-1080 cells was performed. Cancer cell migration-related proteins were identified by obtaining a 2-dimensional gel electrophoresis (2-DE) in total cellular protein profile of blue LED-irradiated cancer cells, followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of proteins. Protein levels were examined by immunoblotting. Irradiation with blue LED inhibited CT-26 and HT-1080 cell migration and invasion. The anti-metastatic effects of blue LED irradiation were associated with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression. P38 MAPK phosphorylation was increased in blue LED-irradiated CT-26 and HT-1080 cells, but was inhibited after pretreatment with SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK phosphorylation by SB203580 treatment increased number of migratory cancer cells in CT-26 and HT-1080 cells, indicating that blue LED irradiation inhibited cancer cell migration via phosphorylation of p38 MAPK. Additionally blue LED irradiation of mice injected with CT-26 cells expressing luciferase decreased early stage lung metastasis compared to untreated control mice. These results indicate that blue LED irradiation inhibits cancer cell migration and invasion in vitro and in vivo.

Thermohydrogel Containing Melanin for Photothermal Cancer Therapy.

Melanin is an effective absorber of light and can extend to near infrared (NIR) regions. In this study, a natural melanin is presented as a photothermal therapeutic agent (PTA) because it provides a good photothermal conversion efficiency, shows biodegradability, and does not induce long-term toxicity during retention in vivo. Poloxamer solution containing melanin (Pol-Mel) does not show any precipitation and shows sol-gel transition at body temperature. After irradiation from 808 nm NIR laser at 1.5 W cm-2 for 3 min, the photothermal conversion efficiency of Pol-Mel is enough to kill cancer cells in vitro and in vivo. The tumor growth of mice bearing CT26 tumors treated with Pol-Mel injection and laser irradiation is suppressed completely without recurrence postirradiation. All these results indicate that Pol-Mel can become an attractive PTA for photothermal cancer therapy.

Data in support of effect of blue LED irradiation in human lymphoma cells.

As a new and preferred light source for phototherapy, blue light emitting diodes (LEDs) with wavelengths of 400-500 nm have been used to treat hyperbilirubinaemia in infantile jaundice [1]. Recent studies report that blue LED irradiation induces apoptosis by stimulating a mitochondrial pathway and reduces the early growth rate of melanoma cells in mice [2]. Here, we detected the induction of apoptotic cell death and formation of autophagosome in human B lymphoma cells after irradiation with blue LED. This paper provides data in support of the research article entitled "Blue light emitting diode induces apoptosis in lymphoid cells by stimulating autophagy" [3].

Blue light emitting diode induces apoptosis in lymphoid cells by stimulating autophagy.

The present study was performed to examine the induction of apoptotic cell death and autophagy by blue LED irradiation, and the contribution of autophagy to apoptosis in B cell lymphoma A20 and RAMOS cells exposed to blue LED. Irradiation with blue LED reduced cell viability and induced apoptotic cell death, as indicated by exposure of phosphatidylserine on the plasma outside membrane and fragmentation of DNA. Furthermore, the mitochondrial membrane potential increased, and apoptotic proteins (PARP, caspase 3, Bax, and bcl-2) were observed. In addition, the level of intracellular superoxide anion (O2(-)) gradually increased. Interestingly the formation of autophagosomes and level of LC3-II were increased in blue LED-irradiated A20 and RAMOS cells, but inhibited after pretreatment with 3-methyladenine (3-MA), widely used as an autophagy inhibitor. Inhibition of the autophagic process by pretreatment with 3-MA blocked blue LED irradiation-induced caspase-3 activation. Moreover, a significant reduction of both the early and late phases of apoptosis after transfection with ATG5 and beclin 1 siRNAs was shown by the annexin V/PI staining, indicating a crucial role of autophagy in blue LED-induced apoptosis in cells. Additionally, the survival rate of mice irradiated with blue LED after injection with A20 cells increased compared to the control group. Our data demonstrate that blue LED irradiation induces apoptosis via the mitochondrial-mediated pathway, in conjunction with autophagy. Further studies are needed to elucidate the precise mechanism of blue LED-induced immune cell death.