Red Light Combined with Blue Light Irradiation Regulates Proliferation and Apoptosis in Skin Keratinocytes in Combination with Low Concentrations of Curcumin.
- 1Aviation Medicine Research Laboratory, The General Hospital of the Air Force, Beijing, China.
- 2Department of Dermatology, The General Hospital of the Air Force, Beijing, China.
- 3Department of Clinical Examination, The General Hospital of the Air Force, Beijing, China.
Curcumin is a widely known natural phytochemical from plant Curcuma longa. In recent years, curcumin has received increasing attention because of its capability to induce apoptosis and inhibit cell proliferation as well as its anti-inflammatory properties in different cancer cells. However, the therapeutic benefits of curcumin are severely hampered due to its particularly low absorption via trans-dermal or oral bioavailability. Phototherapy with visible light is gaining more and more support in dermatological therapy. Red light is part of the visible light spectrum, which is able to deeply penetrate the skin to about 6 mm, and directly affect the fibroblast of the skin dermis. Blue light is UV-free irradiation which is fit for treating chronic inflammation diseases. In this study, we show that curcumin at low concentrations (1.25-3.12 ?M) has a strong anti-proliferative effect on TNF-?-induced psoriasis-like inflammation when applied in combination with light-emitting-diode devices. The treatment was especially effective when LED blue light at 405 nm was combined with red light at 630 or 660 nm, which markedly amplified the anti-proliferative and apoptosis-inducing effects of curcumin. The experimental results demonstrated that this treatment reduced the viability of human skin keratinocytes, decreased cell proliferation, induced apoptosis, inhibited NF-?B activity and activated caspase-8 and caspase-9 while preserving the cell membrane integrity. Moreover, the combined treatment also down-regulated the phosphorylation level of Akt and ERK. Taken together, our results indicated that the combination of curcumin with LED blue light united red light irradiation can attain a higher efficiency of regulating proliferation and apoptosis in skin keratinocytes.
Lasers Med Sci. 2015 Sep 11. [Epub ahead of print]
The relative antimicrobial effect of blue 405 nm LED and blue 405 nm laser on methicillin-resistant Staphylococcus aureus in vitro.
Masson-Meyers DS1, Bumah VV1, Biener G2, Raicu V2,3, Enwemeka CS4,5.
1College of Health Sciences, University of Wisconsin-Milwaukee, 2400 East Hartford Ave., Milwaukee, WI, 53211, USA.
2Department of Physics, University of Wisconsin-Milwaukee, 1900 East Kenwood Blvd., Milwaukee, WI, 53211, USA.
3Department of Biological Sciences, University of Wisconsin-Milwaukee, 3209 North Maryland Ave., Milwaukee, WI, 53211, USA.
4College of Health Sciences, University of Wisconsin-Milwaukee, 2400 East Hartford Ave., Milwaukee, WI, 53211, USA. email@example.com.
5San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182, USA. firstname.lastname@example.org.
It has long been argued that light from a laser diode is superior to light from a light-emitting diode (LED) in terms of its effect on biological tissues. In order to shed light on this ongoing debate, we compared the antimicrobial effect of light emitted from a 405-nm LED with that of a 405-nm laser on methicillin-resistant Staphylococcus aureus (MRSA) at comparable fluences. We cultured 5?×?106 CFU/ml MRSA on tryptic soy agar and then irradiated culture plates once, twice, or thrice with either LED or laser light using 40, 54, 81, or 121 J/cm2 fluence at 15-, 30-, or 240-min time interval between irradiation. Cultures were incubated immediately after irradiation at 37 °C for 24 h before imaging and counting remnant bacterial colonies. Regardless of the device used, LED or laser, irradiation at each fluence resulted in statistically significant bacterial growth suppression compared to non-irradiated controls (p?<?0.0001). The antimicrobial effect of both light sources, LED and laser, was not statistically different at each fluence in 35 of the 36 experimental trials. Bacterial growth suppression achieved with either source of light increased with repeated irradiation, particularly at the 15- or 30-min treatment time interval. Thus, we conclude that the antimicrobial effect of 405-nm laser and 405-nm LED on MRSA is similar; neither has a superior antimicrobial effect when compared to the other.
Dynamics of autonomic regulation and daily pH-metry in patients with gastroesophageal reflux disease under the influence of low-intensity laser irradiation of blood.
102 patients with GERD were examined: 70 female (68%) and 32 men (32%). Age of respondents ranged from 20 to 65 years (average of 45.8 ±8,2). All patients were randomly divided into 2 groups. In the first (control) group (30 people) traditional drug treatment were used according to the standard therapy of GERD (proton pump inhibitors, antacids, prokinetics), patients in the second (main) group (70 people) along with drug therapy has received a course of intravenous laser therapy according to the methods ILIB-405. For intravenous laser treatment Russian apparatus “Matrix-ILIB” (“Matrix”, Russia) was used with wavelength 0,405 ?m, output power at the end of the main optical path of 1-1.5 mW. Laser blood irradiation was carried out for 15 minutes in the CW mode, the course of treatment was 10 daily treatments with a break on Saturday and Sunday. Conclusions: 1. Intravenouslaser irradiation of blood in the complex therapy of patients with gastroesophageal reflux disease improved significantly of HRV due to the alignment of parasympathetic regulation circuit and reducing the activity of sympathetic autonomic regulation, 2. the inclusion of intravenous laser irradiation of blood in the complex therapy of patients with GERD was accompanied by reliable normalization of the indicators of the daily pH-metry of the esophagus in patients with GERD.
Wavelength and Bacterial Density Influence the Bactericidal Effect of Blue Light on Methicillin-Resistant Staphylococcus aureus (MRSA).
- 1 College of Health Sciences, University of Wisconsin-Milwaukee , Milwaukee, Wisconsin.
Abstract Objective: The purpose of this study was to investigate the effect of wavelength and methicillin-resistant Staphylococcus aureus (MRSA) density on the bactericidal effect of 405 and 470?nm light. Background data: It is recognized that 405 and 470?nm light-emitting diode (LED) light kill MRSA in standard 5×10(6) colony-forming units (CFU)/mL cultures; however, the effect of bacterial density on the bactericidal effect of each wavelength is not known.
Methods: In three experiments, we cultured and plated US300 MRSA at four densities. Then, we irradiated each plate once with either wavelength at 0, 1, 3, 45, 50, 55, 60, and 220?J/cm(2).
Results: Irradiation with either wavelength reduced bacterial colonies at each density (p<0.05). More bacteria were cleared as density increased; however, the proportion of colonies cleared, inversely decreased as density increased-the maximum being 100%, 96%, and 78% for 3×10(6), 5×10(6), and 7×10(6) CFU/mL cultures, respectively. Both wavelengths had similar effects on the sparser 3×10(6) and 5×10(6) CFU/mL cultures, but in the denser 7×10(6) CFU/mL culture, 405?nm light cleared more bacteria at each fluence (p<0.001). To determine the effect of beam penetration, denser 8×10(6) and 12×10(6) CFU/mL culture plates were irradiated either from the top, the bottom, or both directions. More colonies were eradicated from plates irradiated from top and bottom, than from plates irradiated from top or bottom at the same sum total fluences (p<0.001).
Conclusions: The bactericidal effect of LED blue light is limited more by light penetration of bacterial layers than by bacterial density per se.
Photomed Laser Surg. 2013 Feb 7. [Epub ahead of print]
Blue Laser Irradiation Generates Intracellular Reactive Oxygen Species in Various Types of Cells.
Department of Medical Engineering, National Defence Medical College , Saitama, Japan .
Abstract Objective: The purpose of this study was to measure intracellular reactive oxygen species (ROS) production after laser irradiation in various types of cells.
Background data: ROS are considered to be the key secondary messengers produced by low-level laser therapy (LLLT). Although various mechanisms for the effects of LLLT have been proposed, and intracellular ROS were indicated as the one of the key factors, direct measurement of intracellular ROS of several types of cells after different wavelength lasers irradiation has not been reported.
Materials and methods: Various types of cells were used in this study: mouse preadipocytes (3T3-L1), prechondrocytes (ATDC5), myoblasts (C2C12), mesenchymal stromal cells (KUSA-A1), lung cancer cells (LLC), insulinoma cells (MIN6), fibroblasts (NIH-3T3), human cervix adenocarcinoma cells (HeLa), macrophages differentiated from lymphocytes (THP-1) after treatment with phorbol ester, and rat basophilic leukemia cells (RBL-2H3). Cells were irradiated with a blue laser (wavelength: 405?nm), a red laser (wavelength: 664?nm) or a near infrared laser (wavelength: 808?nm) at 100 mW/cm(2) for 60 or 120?sec. Intracellular ROS levels were measured by fluorometric assay using the intracellular ROS probe, CM-H(2)DCFDA in a flow cytometer.
Results: After a blue laser irradiation, intracellular ROS levels were increased in all types of cells. In contrast, intracellular ROS generation was not observed after irradiation with a red laser or near-infrared laser.
Conclusions: Potential sources of intracellular ROS were excited by blue laser irradiation, resulting in ROS production within cells. Although the low-level intracellular ROS should be generated after a red or a near-infrared laser irradiation, the only high level intracellular ROS were detected by the ROS probe used in this study. As ROS are considered to be key secondary messengers, the specific functional regulation of cells by laser irradiation will be studied in a future study.
BMC. Microbiol. 2012 Aug 15;12(1):176. [Epub ahead of print]
Inhibitory effects of 405 nm irradiation on Chlamydia trachomatis growth and characterization of the ensuing inflammatory response in HeLa cells.
Chlamydia trachomatis is an intracellular bacterium that resides in the conjunctival and reproductive tract mucosae and is responsible for an array of acute and chronic diseases. A percentage of these infections persist even after use of antibiotics, suggesting the need for alternative treatments. Previous studies have demonstrated anti-bacterial effects using different wavelengths of visible light at varying energy densities, though only against extracellular bacteria. We investigated the effects of visible light (405 and 670 nm) irradiation via light emitting diode (LEDs) on chlamydial growth in end cervical epithelial cells, HeLa, during active and penicillin-induced persistent infections. Furthermore, we analyzed the effect of this photo treatment on the ensuing secretion of IL-6 and CCL2, two pro-inflammatory cytokines that have previously been identified as immunopathologic components associated with trichiasis in vivo.
C. trachomatis-infected HeLa cells were treated with 405 or 670 nm irradiation at varying energy densities (0 — 20 J/cm2). Bacterial growth was assessed by quantitative real-time PCR analyzing the 16S: GAPDH ratio, while cell-free supernatants were examined for IL-6 and Monocyte chemoattractant protein-1 (CCL2) production. Our results demonstrated a significant dose-dependent inhibitory effect on chlamydial growth during both active and persistent infections following 405 nm irradiation. Diminished bacterial load corresponded to lower IL-6 concentrations, but was not related to CCL2 levels. In vitro modeling of a persistent C. trachomatis infection induced by penicillin demonstrated significantly elevated IL-6 levels compared to C. trachomatis infection alone, though 405 nm irradiation had a minimal effect on this production.
Together these results identify novel inhibitory effects of 405 nm violet light on the bacterial growth of intracellular bacterium C. trachomatis in vitro, which also coincides with diminished levels of the pro-inflammatory cytokine IL-6.
Photomed Laser Surg. 2009 Apr;27(2):221-6.
Blue 470-nm light kills methicillin-resistant Staphylococcus aureus (MRSA) in vitro.
Enwemeka CS, Williams D, Enwemeka SK, Hollosi S, Yens D.
School of Health Professions, Behavioral, and Life Sciences, New York Institute of Technology, Old Westbury, New York 11568-8000, USA.Enwemeka@nyit.edu
BACKGROUND DATA: In a previous study, we showed that 405-nm light photo-destroys methicillin-resistant Staphylococcus aureus (MRSA). The 390-420 nm spectral width of the 405-nm superluminous diode (SLD) source may raise safety concerns in clinical practice, because of the trace of ultraviolet (UV) light within the spectrum.
OBJECTIVE: Here we report the effect of a different wavelength of blue light, one that has no trace of UV, on two strains of MRSA–the US-300 strain of CA-MRSA and the IS-853 strain of HA-MRSA–in vitro.
MATERIALS AND METHODS: We cultured and plated each strain, and then irradiated each plate with 0, 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 25, 30, 35, 40, 45, 50, 55, or 60 J/cm2 of energy a single time, using a 470-nm SLD phototherapy device. The irradiated specimens were then incubated at 35 degrees C for 24 h. Subsequently, digital images were made and quantified to obtain colony counts and the aggregate area occupied by bacteria.
RESULTS: Photo-irradiation produced a statistically significant dose-dependent reduction in both the number and the aggregate area of colonies formed by each strain (p < 0.001). The higher the dose the more bacteria were killed, but the effect was not linear, and was more impressive at lower doses than at higher doses. Nearly 30% of both strains was killed with as little as 3 J/cm2 of energy. As much as 90.4% of the US-300 and the IS-853 colonies, respectively, were killed with an energy density of 55 J/cm2. This same dose eradicated 91.7% and 94.8% of the aggregate area of the US-300 and the IS-853 strains, respectively.
CONCLUSION: At practical dose ranges, 470-nm blue light kills HA-MRSA and CA-MRSA in vitro, suggesting that a similar bactericidal effect may be attained in human cases of cutaneous and subcutaneous MRSA infections.
Appl Environ Microbiol. 2009 Apr;75(7):1932-7. Epub 2009 Feb 6.
Inactivation of bacterial pathogens following exposure to light from a 405 nanometer light-emitting diode array.
Maclean M, MacGregor SJ, Anderson JG, Woolsey G.
The Robertson Trust Laboratory for Electronic Sterilisation Technologies, University of Strathclyde, 204 George Street, Glasgow, Scotland. email@example.com
This study demonstrates the susceptibility of a variety of medically important bacteria to inactivation by 405-nm light from an array of light-emitting diodes (LEDs), without the application of exogenous photosensitizer molecules. Selected bacterial pathogens, all commonly associated with hospital-acquired infections, were exposed to the 405-nm LED array, and the results show that both gram-positive and gram-negative species were successfully inactivated, with the general trend showing gram-positive species to be more susceptible than gram-negative bacteria. Detailed investigation of the bactericidal effect of the blue-light treatment on Staphylococcus aureus suspensions, for a range of different population densities, demonstrated that 405-nm LED array illumination can cause complete inactivation at high population densities: inactivation levels corresponding to a 9-log(10) reduction were achieved. The results, which show the inactivation of a wide range of medically important bacteria including methicillin-resistant Staphylococcus aureus, demonstrate that, with further development, narrow-spectrum 405-nm visible-light illumination from an LED source has the potential to provide a novel decontamination method with a wide range of potential applications.
Photomed Laser Surg. 2006 Dec;24(6):684-8
In vitro bactericidal effects of 405-nm and 470-nm blue light.
Guffey JS, Wilborn J.
Physical Therapy Plus, Bauxite, Arkansas 72011, USA. firstname.lastname@example.org
OBJECTIVE: The aim of this study was to determine the bactericidal effect of 405- and 470-nm light on two bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, in vitro.
BACKGROUND DATA: It is well-known that UV light kills bacteria, but the bactericidal effects of UV may not be unique since recent studies indicate that blue light produces a somewhat similar effect. The effects of blue light seem varied depending on wavelength, dose and the nature of the bacteria, hence this study.
METHODS: Two common aerobes, Staphylococcus aureus and Pseudomonas aeruginosa, and anaerobic Propionibacterium acnes were tested. Each organism was treated with Super Luminous Diode probes with peak emission at 405 and 470 nm. Treatment was timed to yield 1, 3, 5, 10, and 15 Jcm2 doses. Colony counts were performed and compared to untreated controls.
RESULTS: The 405-nm light produced a dose dependent bactericidal effect on Pseudomonas aeruginosa and Staphylococcus aureus (p < .05), achieving as much as 95.1% and nearly 90% kill rate for each, respectively. The 470-nm light effectively killed Pseudomonas aeruginosa at all dose levels, but only killed Staphylococcus aureus at 10 and 15 J cm2. With this wavelength, as much as 96.5% and 62% reduction of Pseudomonas aeruginosa and Staphylococcus aureus was achieved, respectively. Neither of the two wavelengths proved bactericidal with anaerobic Propionibacterium acnes.
CONCLUSION: The results indicate that, in vitro, 405- and 470-nm blue light produce dose dependent bactericidal effects on Pseudomonas aeruginosa and Staphylococcus aureus but not Propionibacterium acnes.
Photomed Laser Surg. 2006 Dec;24(6):680-3.
Effects of combined 405-nm and 880-nm light on Staphylococcus aureus and Pseudomonas aeruginosa in vitro.
Guffey JS, Wilborn J.
Physical Therapy Plus, Bauxite, Arkansas 72011, USA. email@example.com
OBJECTIVE: The aim of this study was to determine the effect of a combination of 405-nm blue light and 880-nm infrared light on Staphylococcus aureus and Pseudomonas aeruginosa in vitro.
BACKGROUND DATA: Reports indicate that certain wavelengths and treatment parameters of light promote the growth of bacteria, but our earlier study indicates that light at specific wavelengths and intensities are bactericidal for specific organisms (1).
METHODS: Two common aerobes, Staphylococcus aureus and Pseudomonas aeruginosa were tested because of their frequent isolation from skin infections and wounds. Each organism was treated simultaneously with a combination of 405-nm and 880-nm light emitted by a cluster of Super Luminous Diodes (SLDs). Doses of 1, 3, 5, 10, and 20 Jcm2 were used. Colony counts were performed and compared to untreated controls using Student t tests and one-way ANOVA with Tukey and Scheffe post hoc analyses.
RESULTS: The results revealed significant dose-dependent bactericidal effects of the combined blue and infrared light on Staphylococcus aureus (F 4,94 = 5.38, p = 0.001) and Pseudomonas aeruginosa (F 4,95 = 21.35, p < 0.001). With P. aeruginosa, the treatment reduced the number of bacteria colonies at all doses, achieving statistical significance at 1, 3, and 20 J cm2 doses and reducing bacterial colony by as much as 93.8%; the most effective dose being 20 J cm2. Irradiation of S. aureus resulted in statistically significant decreases in bacterial colonies at all dose levels; the most decrease, 72%, was also achieved with 20 Jcm2.
CONCLUSION: Appropriate doses of combined 405-nm and 880-nm phototherapy can kill Staphylococcus aureus and Pseudomonas aeruginosa in vitro, suggesting that a similar effect may be produced in clinical cases of bacterial infection.
Med Microbiol. 1995 Jan;42(1):62-6
Killing of methicillin-resistant Staphylococcus aureus by low-power laser light.
Wilson M, Yianni C.
Department of Microbiology, Eastman Dental Institute for Oral Health Sciences, University of London.
The purpose of this study was to determine whether a methicillin-resistant strain of Staphylococcus aureus (MRSA) could be sensitised by toluidine blue O (TBO) to killing by light from a low-power helium/neon (HeNe) laser. Suspensions containing c. 10(10) cfu of MRSA were irradiated with light from a 35 mW HeNe laser (energy dose: 0.5-2.1 J) in the presence of TBO (1.6-12.5 micrograms/ml) and the survivors were enumerated. The kills attained depended on both the light energy dose and concentration of TBO employed. A 4.47 log10 reduction in the viable count was achieved with a TBO concentration of 12.5 micrograms/ml and a light dose of 2.1 J (energy density 43 J/cm2). MRSA were susceptible to killing by the laser light within 30 s of exposure to the TBO. The results of this study have demonstrated that MRSA can be rapidly sensitised by TBO to killing by HeNe laser light and that killing depends on the light energy dose and sensitiser concentration.