Timon Cheng-Yi Liu

Photobiomodulation: phenomenology and its mechanism

There are two kinds of pathways mediating cellular photobiomodulation, the specific one is mediated by the resonant interaction of light with molecules such as cytochrome nitrosyl complexes of mitochondrial electron transfer chain, singlet oxygen, hemoglobin or photosensentor such as endogenous porphyrines, the non-specific one is mediated by the non-resonant interaction of light with membrane proteins. Some of specific pathways mediating photobiomodulation can damage membrane or cell compartments such as mitochondria, lysosomes, endoplasmic reticulum by photodynamic damage if the light intensity is very high so that photodynamic damage will limit the maximum intensity of the light of photobiomodulation although the non-specific pathways mediating photobiomodulation might not damage cells. As the reciprocity law, the rule of Bunsen and Roscoe, was not obeyed for almost all the studied photobiomodulation, and the light energy reaps the greatest benefit where it is most needed, photobiomodulation was thought to be dominantly mediated by the non-specific pathways although the specific pathways can act as a role, which is supported by the dose relationship research in which the photobiomodulation effects were found to be the SIN function of radiation time in many works on the dose relationship when the intensity is kept constant. The non-specific pathways were mainly mediated by membrane receptors and the ultraweak non-resonant interaction of light with membrane receptors can be physically amplified by the coherent state of membrane receptors and then chemically exemplified by signal transduction according to our biological information model of photobiomodulation supported by its successful cellular, animal and clinic applications.

Information biology on low intensity laser irradiation effects on red blood cells

The cytochrome absorption makes the photon act as a carrier of biological energy as the cytochrome system in the mitochondria can absorb the photon and stimulate electron transport, which generates bioenergy in the form of ATP from ADP. Many feel that the respiratory chain is at the base of any effects that laser therapy might have. However, there is a kind of effect of He-Ne laser irradiation on red blood cells (RBC) in which there is no mitochondria. In other words, the photon acts also as a carrier of biological information. Recently, Liu et al have studied the information biology on low intensity laser by use of time approach on generation of biological information, and put forward the membrane-receptor-mediated signal transduction mechanism, i.e., the biological information model of low- intensity laser (BIML) and the biological information transformation model (BITML), to explain the biomodulation function. As the frequency of the absorption light of membrane receptors is greater than the one of visible laser irradiation, the membrane absorption of visible light is non-resonant, and its transition rate is extraordinarily small, but can be amplified by the coherent state of the identical and independent membrane receptors of a pathological cell. In this paper, we apply these results to study Information biology on low intensity laser irradiation effects on RBC.

Randomized trial comparing exercise therapy, alternating cold and hot therapy, and low intensity laser therapy for chronic lumbar muscle strain

The purpose of this study was to compare the effects of exercise therapy, alternating cold and hot (ACH) therapy and low intensity laser (LIL) therapy in patients with chronic lumbar muscle strain (CLMS). Thirty-two patients were randomly allocated to four groups: exercise group, ACH group, LIL group, and combination group of exercise, ACH and LIL, eight in each group. Sixteen treatments were given over the course of 4 weeks. Lumbar muscle endurance, flexion and lateral flexion measures, visual analogue scale (VAS) and lumbar disability questionnaire (LDQ) were used in the clinical and functional evaluations before, immediately after, and 4 weeks after treatment. It was found that the values of endurance, VAS and LDQ in all groups were significantly improved from before to after treatment (P < 0.01). The combination group showed significantly larger reduction on pain level and functional disability than the other groups immediately and 4 weeks after treatment (P < 0.01). Pain level reduced significantly more in the ACH group than in the exercise group or the LIL group immediately and 4 weeks after treatment (P < 0.05). Lumbar muscle endurance and spinal ranges of motion in all groups were improved after treatment but there was no significant difference between any therapy groups. In conclusion, exercise therapy, ACH therapy and LIL therapy were effective in the treatment of CLMS. ACH therapy was more effective than exercise therapy or LIL therapy. The combination therapy of exercise, ACH and LIL had still better rehabilitative effects on CLMS.

PHOTOBIOMODULATION ON SPORTS INJURIES

Sports injuries healing has long been an important field in sports medicine. The stimulatory effects of Low intensity laser (LIL) irradiation have been investigated in several medical fields, such as cultured cell response, wound healing, hormonal or neural stimulation, pain relief and others. The aim of this study was to evaluate whether LIL irradiation can accelerate sports injuries healing. Some experimental and clinical studies have shown the laser stimulation effects on soft tissues and cartilage, however, controversy still exists regarding the role of LIL when used as a therapeutic device. Summarizing the data of cell studies and animal experiments and clinic trials by using the biological information model of photobiomodulation, we conclude that LIL irradiation is a valuable treatment for superficial and localized sports injuries and that the injuries healing effects of the therapy depend on the dosage of LIL irradiation.

Information biology of laser acupuncture

Laser acupuncture as an alternative, noninvasive, painless and cost-effective therapy is widely used for acute and chronic pain, nausea, circulatory functions, and mood-related behavioral disorders. It was suggested one of the pathways mediated laser acupuncture was from laser biomodulation on acupuncture point cells to autonomic nervous subsystems through meridian. As laser irradiation used for acupuncture is red or infra red, we put forward the following model: at dose 1(100-3 J/m2), the irradiation activates parasympathetic nervous subsystem (PSN); at dose 2(103-5 J/m2), the irradiation activates sympathetic nervous subsystem (SN); at dose 3(105-6 J/m2), the irradiation activates PSN; and at dose 4(106-7 J/m2), the irradiation activates SN. This model was verified by its successful applications.

Biomodulation of light on cells in laser surgery

In laser surgery, it has been observed pulsed 532-nm laser can avoid postoperative purpura, but pulsed 585-nm, 595-nm or 600-nm lasers nonetheless cause purpura when they were used to treat port-wine stains; the XeCl excimer laser (308 nm) can safely and effectively clear psoriasis; both XeCl excimer laser and Ho:YAG laser were used in coronary interventions, but only former was approved by the FDA; open channels after ultraviolet (UV) laser treatment and closed channels with infrared (IR) lasers for transmyocardial laser revascularization; and so on. In this paper, the biological information model of low intensity laser (BIML) is extended to include UVA biomodulation and is used to understand these phenomena. Although the central intensity of the laser beam is so intense that it destroys the tissue, the edge intensity is so low that it can induce biomodulation. Our investigation showed that biomodulation of light on cells might play an important role in the long-term effects of laser surgery.

Low intensity laser treatment of nerve injuries

The neural regeneration and functional recovery after nerve injuries has long been an important field in neuroscience. Low intensity laser (LIL) irradiation is a novel and useful tool for the treatment of many injuries and disorders. The aim of this study was to assess the role of LIL irradiation in the treatment of peripheral and central nerve injuries. Some animal experiments and clinical investigations have shown beneficial effects of LIL irradiation on neural tissues, but its therapeutic value and efficacy are controversial. Reviewing the data of experimental and clinical studies by using the biological information model of photobiomodulation, we conclude that LIL irradiation in specific parameters can promote the regeneration of injured peripheral and central nerves and LIL therapy is a safe and valuable treatment for superficial peripheral nerve injuries and spinal cord injury. The biological effects of LIL treatment depend largely on laser wavelength, power and dose per site and effective irradiation doses are location-specific.

SPECT study of low intensity He-Ne laser intravascular irradiation therapy for brain infarction

We used single photon emission computed tomography (SPECT) in brain perfusion imaging to study the changes of regional cerebral blood flow (rCBF) and cerebral function in brain infarction patients treated with intravascular laser irradiation of blood (ILIB). 17 of 35 patients with brain infarction were admitted to be treated by ILIB on the base of standard drug therapy, and SPECT brain perfusion imaging was performed before and after ILIB therapy with self-comparison. The results were analyzed in quantity with brain blood flow function change rate (BFCR%) model. Effect of ILIB during the therapy process in the other 18 patients were also observed. In the 18 patients, SPECT indicated an improvement of rCBF (both in focus and in total brain) and cerebral function after a 30 min-ILIB therapy. And the 17 patients showed an enhancement of total brain rCBF and cerebral function after ILIB therapy in comparison with that before, especially for the focus side of the brain. The enhancement for focus itself was extremely obvious with a higher significant difference (P<0.0001). The mirror regions had no significant change (P>0.05). BFCR% of foci was prominently higher than that of mirror regions (P<0.0001). In conclusion, the ILIB therapy can improve rCBF and cerebral function and activate brain cells of patients with brain infarction. The results denote new evidence of ILIB therapy for those patients with cerebral ischemia.

The membrane receptor mediated signal transduction mechanism of low-intensity light effects on fibroblast

The membrane receptor mediated signal transduction mechanism (STM) on photobiomodulation was suggested by Liu et al, and verified by successful applications. In this paper, it was used to study photobiomodulation on fibroblasts. As the frequency of the absorption light of membrane receptors is greater than the light from UVA to IR, the membrane absorption of the light is non-resonant, and its transition rate is extraordinarily small, but can be amplified by the coherent state of the identical and independent membrane receptors. The activation coherent states of receptors will activate signal transduction pathway, which was called collective phototransduction. It was shown that collective phototransduction mediated STM was one of the possible mechanisms of photobiomodulation on fibroblasts.

The mechanism of PDT-induced apoptosis

Photodynamic therapy (PDT) can induce apoptosis in many cancer cells in vitro and in tumors in vivo. Cells become more oxidation with PDT, and maintain differentiation and proliferation, go apoptosis and necrosis with the increase of reactive oxygen species (ROS) concentration. ROS can induce apoptosis through mitochondria by inhibiting respiration chain or oxidative phosphorylation or damaging mitochondrial membrane. ROS can initiate apoptosis through endoplamic reticulum(ER) by opening Ca2+ channel or starting unfold protein response (UPR). ROS can also induce apoptosis through Golgi by producing ganglioside GD3 by use of ceramide, which induces apoptosis by activating caspase-3, JNK and p38 MAPK. It can also induce apoptosis by activating Bip (mitochondria-dependant) or preocaspase-12 (mitochondria- independent) or inhibiting protein synthesizing. There are so complicated cross-talking among different signal pathways or organnells that we think PDT-induced apoptosis is mediated by multiplex pathways and excessive levels in a refined network.