Role of 904 nm superpulsed laser-mediated photobiomodulation on nitroxidative stress and redox homeostasis in burn wound healing.

BACKGROUND: Burn wound healing is delayed due to several critical factors such as sustained inflammation, vascular disorder, neuropathy, enhanced proteolysis, infection, and oxidative stress. Burn wounds have limited oxygen supply owing to compromised blood circulation. Hypoxic burn milieu leads to free radicals overproduction incurring oxidative injury, which impedes repair process causing damage to cell membranes, proteins, lipids, and DNA. Photobiomodulation (PBM) with 904 nm superpulsed laser had shown potent healing efficacy via attenuating inflammation while enhancing proliferation, angiogenesis, collagen accumulation, and bioenergetic activation in burn wounds. METHODS: This study investigated the effects of 904 nm superpulsed laser at 0.4 mW/cm2 average power density, 0.2 J/cm2 total energy density, 100 Hz frequency, and 200 ns pulse width for 10 min daily for seven days postburn injury on nitroxidative stress, endogenous antioxidants status, and redox homeostasis. RESULTS: Photobiomodulation treatment significantly decreased reactive oxygen species, nitric oxide, and lipid peroxidation levels as compared to non-irradiated control. Further, protective action of PBM against protein oxidative damage was evidenced by reduced protein carbonylation and advanced oxidation protein product levels along with significantly enhanced endogenous antioxidants levels of SOD, catalase, GPx, GST, reduced glutathione, and thiol (T-SH, Np-SH, P-SH). Biochemical changes aid in reduction of oxidative stress and maintenance of redox homeostasis, which further well corroborated by significantly up-regulated protein expression of Nrf 2, hemeoxygenase (HO-1), and thioredoxin reductase 2 (Txnrd2). CONCLUSION: Photobiomodulation with 904 nm superpulsed laser led to reduction of nitroxidative stress, induction of endogenous antioxidants, and maintenance of redox homeostasis that could play a vital role in augmentation of burn wound healing.

The 808 nm and 980 nm infrared laser irradiation affects spore germination and stored calcium homeostasis: A comparative study using delivery hand-pieces with standard (Gaussian) or flat-top profile.

Photobiomodulation relies on the transfer of energy from incident photons to a cell photoacceptor. For many years the concept of photobiomodulation and its outcome has been based upon a belief that the sole receptor within the cell was the mitochondrion. Recently, it has become apparent that there are other photoacceptors operating in different regions of the electromagnetic spectrum. Alternative photoacceptors would appear to be water and mechanisms regulating calcium homeostasis, despite a direct effect of laser photonic energy on intracellular calcium concentration outwith mitochondrial activity or influence, have not been clearly demonstrated. Therefore, to increase the knowledge of intracellular­calcium and laser photon interaction, as well as to demonstrate differences in irradiation profiles with modern hand-pieces, we tested and compared the photobiomodulatory effect of 808 nm and 980 nm diode laser light by low- and higher-energy (60s, 100 mW/cm2, 100 mW/cm2, 500 mW/cm2, 1000 mW/cm2, 1500 mW/cm2, 2000 mW/cm2) irradiated with a "standard" (Gaussian fluence distribution) hand-piece or with a "flat-top" (uniform fluence) hand-piece. For this purpose, we used the eukaryote unicellular-model Dictyostelium discoideum. The 808 nm and 980 nm infrared laser light, at the energy tested directly affect the stored Ca2+ homeostasis, independent of the mitochondrial respiratory chain activities. From an organism perspective, the effect on Ca2+-dependent signal transduction as the regulator of spore germination in Dictyostelium, demonstrates how a cell can respond quickly to the correct laser photonic stimulus through a different cellular pathway than the known light-chromophore(mitochondria) interaction. Additionally, both hand-piece designs tested were able to photobiomodulate the D. discoideum cell; however, the hand-piece with a flat-top profile, through uniform fluence levels allows more effective and reproducible effects.

Seasonal consumption of polyphenol-rich fruits affects the hypothalamic leptin signaling system in a photoperiod-dependent mode.

Leptin has a central role in the maintenance of energy homeostasis, and its sensitivity is influenced by both the photoperiod and dietary polyphenols. The aim of this study was to investigate the effect of seasonal consumption of polyphenol-rich fruits on the hypothalamic leptin signaling system in non-obese and obese animals placed under different photoperiods. Non-obese and diet-induced obese male Fischer 344 rats were placed under either a short-day (SD) or long-day (LD) photoperiod and were supplemented with either 100 mg/kg of lyophilized red grapes or cherries. In non-obese animals, both fruits reduced energy balance independent of the photoperiod to which they were placed. However, the hypothalamic gene expression of Pomc was significantly up-regulated only in the SD photoperiod. In contrast, in obese animals only cherry significantly decreased the energy balance, although both fruits were able to counteract the diet-induced increase in hypothalamic AgRP mRNA levels when consumed during the SD photoperiod. In conclusion, the consumption of rich-polyphenol fruits may increase leptin sensitivity through the modulation of the hypothalamic leptin signal pathway mainly when consumed in the SD photoperiod. Therefore, fruit seasonality should be considered, as it can influence energy homeostasis and obesity.

Photobiomodulation induces antinociception, recovers structural aspects and regulates mitochondrial homeostasis in peripheral nerve of diabetic mice.

Diabetic peripheral neuropathy (DPN) is a nervous disorder caused by diabetes mellitus, affecting about 50% of patients in clinical medicine. Chronic pain is one of the major and most unpleasant symptoms developed by those patients, and conventional available treatments for the neuropathy, including the associated pain, are still unsatisfactory and benefit only a small number of patients. Photobiomodulation (PBM) has been gaining clinical acceptance once it is able to promote early nerve regeneration resulting in significant improvement in peripheral nerves disabilities. In this work, the effects of PBM (660 nm, 30 mW, 1.6 J/cm2 , 0.28 cm2 , 15 s in a continuous frequency) on treating DPN-induced pain and nerve damage were evaluated in an experimental model of diabetic-neuropathy induced by streptozotocin in mice. PBM-induced antinociception in neuropathic-pain mice was dependent on central opioids release. After 21 consecutive applications, PBM increased nerve growth factor levels and induced structural recovery increasing mitochondrial content and regulating Parkin in the sciatic nerve of DPN-mice. Taking together, these data provide new insights into the mechanisms involved in the effects of PBM-therapy emphasizing its therapeutic potential in the treatment of DPN.

Osteoradionecrosis of the jaws: case series treated with adjuvant low-level laser therapy and antimicrobial photodynamic therapy.

BACKGROUND: Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa. METHODS: We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years. RESULTS: 100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa. CONCLUSION: LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ.

Osteoradionecrosis of the jaws: case series treated with adjuvant low-level laser therapy and antimicrobial photodynamic therapy

Abstract Background: Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa. Methods: We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years. Results: 100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa. Conclusion: LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ.

Extremely low-frequency electromagnetic field induces neural differentiation of hBM-MSCs through regulation of (Zn)-metallothionein-3.

Extremely low-frequency electromagnetic field (ELFEMF) can stimulate neural differentiation in human bone marrow-derived mesenchymal cells (hBM-MSCs), and this provides an opportunity for research on neurodegenerative diseases such as Alzheimer's disease (AD). Metallothionein-3 (MT3), an isoform of the metal-binding proteins, metallothioneins, involved in maintaining intracellular zinc (Zn) homeostasis and the deregulation of zinc homeostasis, has separately been implicated in AD. Here, we investigated the effect of ELFEMF-induced neural differentiation of hBM-MSCs on Zn-MT3 homeostatic interaction. Exposure to ELFEMF induced neural differentiation of hBM-MSCs, which was characterized by decreased proliferation and enhanced neural-like morphology. We observed expression of neuronal markers such as ß-tubulin3, pleiotrophin, and neurofilament-M at the mRNA level and MAP2 at the protein level. ELFEMF-induced neural differentiation correlated with decreased expression of metal-response element-transcription factor 1 and MT3, as well as decreased intracellular Zn concentration. In addition, upregulation of dihydropyrimidinase-related protein 2 was observed, but there was no change in γ-enolase expression. These data indicate a possible regulatory mechanism for MT3 during neural differentiation. Our findings provide considerable insight into molecular mechanisms involved in neural differentiation, which is useful for developing new treatments for neurodegenerative diseases. Bioelectromagnetics. 38:364-373, 2017. © 2017 Wiley Periodicals, Inc.

Extremely low-frequency electromagnetic field exposure enhances inflammatory response and inhibits effect of antioxidant in RAW 264.7 cells.

In recent years, there has been a dramatic increase in the number and variety of electronic devices that emit electromagnetic waves. Because people live and work in close proximity to these pieces of electrical equipment, there is growing concern surrounding the destruction of homeostasis by electromagnetic field exposure. In the present study, the effects of 60 Hz 0.8 mT extremely low-frequency electromagnetic fields (ELF-EMF) on a macrophage cell line (RAW 264.7) were examined. Under defined ELF-EMF exposure conditions, the production of nitric oxide and pro-inflammatory cytokines, TNF-α, IL-1ß, and IL-6, were increased in RAW 264.7 cells and the expression of those genes was also upregulated. However, cell proliferation was not altered. Translocation of NF-κB (nuclear factor kappa B), molecules that act downstream of the pro-inflammatory cytokines, were increased to the nucleus under ELF-EMF exposure conditions. In addition, we found that ELF-EMF exposure elevated activation of nuclear factor of activated T cells (NFAT) 2, as well as positively affected the influx of calcium. Furthermore, with both the presence of a potent antioxidant (Resveratrol) and downregulation of the antioxidant-related gene Prx-1 (Peroxiredoxin-1), ELF-EMF was associated with higher inflammatory responses of macrophages. These results suggest that an ELF-EMF amplifies inflammatory responses through enhanced macrophage activation and can decrease the effectiveness of antioxidants. Bioelectromagnetics. 38:374-385, 2017. © 2017 Wiley Periodicals, Inc.

Changes in brain peptides associated with reproduction and energy homeostasis in photosensitive and photorefractory migratory redheaded buntings.

Present study examined the expression of brain peptides associated with the reproduction and energy homeostasis (GnRH/GnIH, NPY/VIP), and assessed their possible functional association in the photosensitive (non-breeding, pre-breeding), photostimulated (breeding) and photorefractory (post-breeding) migratory redheaded buntings (Emberiza bruniceps), using double-labeled immunohistochemistry. Particularly, we measured immunoreactive (-ir) cell numbers, per cent cell area and cell optical density (OD) in the preoptic area (GnRH-I), midbrain (GnRH-II), paraventricular nucleus (GnIH), dorsomedial hypothalamus, DMH and infundibular complex, INc (NPY and VIP), and lateral septal organ (VIP) of buntings kept under natural photoperiods at the wintering latitude (26°55'N). There was a significant seasonal difference in GnRH-I, not GnRH-II, with reduced -ir cells in the photosensitive and photorefractory buntings, and notably with increased cell OD between the refractory and non-breeding states with no increase in testis size. Also, increased cell OD of GnIH neurons in non-breeding state indicated its role in the maintenance of small testes during the post-refractory period. Overall, seasonal changes in GnRH-I and GnIH were found consistent with their suggested roles in reproductive regulation of absolute photorefractory birds. Further, there was a significant seasonal change in cell OD of NPY neurons in DMH, not the INc. In contrast, VIP immunoreactivity was seasonally altered, with a significantly higher VIP-ir cells in breeding than the pre-breeding state. Finally, close proximity between perikarya with fibres suggested functional interactions between the GnRH and GnIH, and NPY and VIP. Thus, seasonal plasticity of brain peptides is perhaps the part of neural regulation of seasonal reproduction and associated energy homeostasis in migratory songbirds.

The effect of low dose ionizing radiation on homeostasis and functional integrity in an organotypic human skin model.

Outside the protection of Earth's atmosphere, astronauts are exposed to low doses of high linear energy transfer (LET) radiation. Future NASA plans for deep space missions or a permanent settlement on the moon are limited by the health risks associated with space radiation exposures. There is a paucity of direct epidemiological data for low dose exposures to space radiation-relevant high LET ions. Health risk models are used to estimate the risk for such exposures, though these models are based on high dose experiments. There is increasing evidence, however, that low and high dose exposures result in different signaling events at the molecular level, and may involve different response mechanisms. Further, despite their low abundance, high LET particles have been identified as the major contributor to health risk during manned space flight. The human skin is exposed in every external radiation scenario, making it an ideal epithelial tissue model in which to study radiation induced effects. Here, we exposed an in vitro three dimensional (3-D) human organotypic skin tissue model to low doses of high LET oxygen (O), silicon (Si) and iron (Fe) ions. We measured proliferation and differentiation profiles in the skin tissue and examined the integrity of the skin's barrier function. We discuss the role of secondary particles in changing the proportion of cells receiving a radiation dose, emphasizing the possible impact on radiation-induced health issues in astronauts.

Pectins, ROS homeostasis and UV-B responses in plant roots.

Light from the sun contains far-red, visible and ultra violet (UV) wavelength regions. Almost all plant species have been evolved under the light environment. Interestingly, several photoreceptors, expressing both in shoots and roots, process the light information during the plant life cycle. Surprisingly, Arabidopsis root apices express besides the UVR8 UV-B receptor, also root-specific UV-B sensing proteins RUS1 and RUS2 linked to the polar cell-cell transport of auxin. In this mini-review, we focus on reactive oxygen species (ROS) signaling and possible roles of pectins internalized via endocytic vesicle recycling system in the root-specific UV-B perception and ROS homeostasis.

Effects of low-level laser therapy on ROS homeostasis and expression of IGF-1 and TGF-ß1 in skeletal muscle during the repair process.

The aim of the present study was to determine the effects of low-level laser therapy (LLLT) on the homeostasis of reactive oxygen species (ROS) and expression of IGF-1 and TGF-ß1 in the gastrocnemius muscles of rats following contusion. Muscle regeneration involves cell proliferation, migration, and differentiation and is regulated by growth factors. A growing body of evidence suggests that LLLT promotes skeletal muscle regeneration and accelerates tissue repair. Adult male Sprague-Dawley rats (n=96) were randomly divided into three groups: control group (no lesion, untreated, n=6), contusion group (n=48), and contusion-plus-LLLT group (n=42). Gallium aluminum arsenide (GaAlAs) laser irradiation (635 nm; beam spot, 0.4 cm(2); output power, 7 mW; power density, 17.5 mW/cm(2); 20 min) was administered to the gastrocnemius contusion for 20 min daily for 10 days. Muscle remodeling was evaluated at 0 h and 1, 2, 3, 7, 14, 21, and 28 days after injury. Hematoxylin and eosin and Van Gieson staining were used to evaluate regeneration and fibrosis; muscle superoxide dismutase (SOD) and malondialdehyde (MDA) were detected via biochemical methods; expression of transforming growth factor beta-1 (TGF-ß1) and insulin-like growth factor-1 (IGF-1) were investigated via immunohistochemistry. The results showed that LLLT markedly promoted the regeneration of muscle and reduced scar formation. LLLT also significantly enhanced muscle SOD activity and significantly decreased muscle MDA levels 1, 2, and 3 days after injury. LLLT increased the expression of IGF-1 2, 3, and 7 days after injury and decreased the expression of IGF-1 21 and 28 days after injury. LLLT decreased the expression of TGF-ß1 3 and 28 days after injury but increased expression at 7 and 14 days after injury. Our study showed that LLLT could modulate the homeostasis of ROS and of the growth factors IGF-1 and TGF-ß1, which are known to play important roles in the repair process. This may constitute a new preventive approach to muscular fibrosis.

Complex interaction of circadian and non-circadian effects of light on mood: shedding new light on an old story.

In addition to its role in vision, light exerts strong effects on behavior. Its powerful role in the modulation of mood is well established, yet remains poorly understood. Much research has focused on the effects of light on circadian rhythms and subsequent interaction with alertness and depression. The recent discovery of a third photoreceptor, melanopsin, expressed in a subset of retinal ganglion cells, allows major improvement of our understanding of how photic information is processed. Light affects behavior in two ways, either indirectly through the circadian timing system, or directly through mechanisms that are independent of the circadian system. These latter effects have barely been studied in regard to mood, but recent investigations on the direct effects of light on sleep and alertness suggest additional pathways through which light could influence mood. Based on our recent findings, we suggest that light, via melanopsin, may exert its antidepressant effect through a modulation of the homeostatic process of sleep. Further research is needed to understand how these mechanisms interplay and how they contribute to the photic regulation of mood. Such research could improve therapeutic management of affective disorders and influence the management of societal lighting conditions.

Differential hypothalamic tyrosine hydroxylase distribution and activation by light in adult mice reared under different light conditions during the suckling period.

In mammals, early light experience during a critical period within the first 3 weeks of postnatal development has long-lasting effects on circadian locomotor activity behaviour and neuropeptide expression in the suprachiasmatic nucleus (SCN) of the hypothalamus, site of the principal pacemaker. Dopamine is thought to be involved in the modulation of photic input within the SCN and in tadpoles, the expression of tyrosine hydroxylase (TH), a rate-limiting enzyme in the synthesis of dopamine, in the SCN is altered by previous light history. We thus hypothesised that dopaminergic neurons may be important for the development of the adapted responses to light that we have previously observed. To test this, we raised mice in either constant darkness, 12:12 h light-dark cycles or constant light during the first 3 weeks after birth, and later examined the expression of TH and FOS in the hypothalamus of these mice as adults, both in the dark and after exposure to a light pulse. We found that early light experience affects TH and FOS expression, both baseline levels and in response to a light pulse, in brain areas which are directly connected to the SCN, and are associated with the circadian control of neuroendocrine function. Therefore, our results suggest that the long-lasting alterations induced by early light environment on several hypothalamic nuclei may be relayed through the SCN, and that TH-expressing cells may play a role in conveying/establishing these alterations. These data suggest a role of early light experience in the regulation of future hormonal homeostasis and circadian behaviour.

[Study of radioprotective effect of "Soma" preparate].

Changes in the functional activity of the synthesis apparatus of rat blood lymphocytes under different scheme in application of bioadditive Soma after acute X-irradiation by fluorescent microspectrometry. Some metabolic indices in animals were investigated too. It has been shown the bioadditive Soma using in norm reliably increased the synthetic activity on days 13 and 20. Preliminary Soma using during a month followed by the same interval increased the animal radioresistance (scheme 1), while the Soma using immediately after irradiation (scheme 2) revealed no pronounced radioprotective effect. It was found the Soma increased metabolism that may be important to recover homeostasis. The results show the expediency of further investigation of the Soma radioprotective properties with different concentrations and schemes as well as the necessity of monitoring the immune system during Soma using.

[Comparative analysis of the influence of various factors in different combinations on the ionic homeostasis of a cell].

The ionic homeostasis is one of the most sensitive tests for the evaluation of functional state of a cell. The agents, which promote elevation of ionic homeostasis, as well as those, which suppress it, are well known. The goal of the present work was tracing the possibilities for altering ionic homeostasis into one or another direction, as a result of combined influence of some agents: ionizing radiation at a dose of 0.1 Gy, EMF with frequency of 45 Hz, 2.0 mT, in one case, and addition to this combination of the homeopathic remedy--stimulated phosphoric acid, at different dilutions. The following data have been obtained: combination of ionizing radiation of 0.1 Gy increased effect against the effect of its constituents, while addition of phosphoric acid at dilution of 10(-14) increased effect even further. In the other series of experiments, combination of ionizing radiation of 0.5 Gy and EMF was used in the same conditions; as a result, the sum effect decreased against its constituents, while addition of highly diluted (10(-200)) phosphoric acid practically arrested this effect. It is concluded that effect of a combined influence depends on a dose of the constituents.

Invited response to definition of hormesis (EJ Calabrese and LA Baldwin).

Calabrese and Baldwin have proposed the Theory of Hormesis to explain a variety of disparate data. We evaluated the explanation using examples of pulmonary injury, radiation injury to white blood cells and selenium as an essential element, reducer of carcinogenesis and a potential toxicant. Calabrese and Baldwin have fulfilled many of the criteria allowing generalizability of their theory. They have gathered data extensively. These data were logically consistent with their experiences. They needed to examine critically the theory and any theories competing with it. At this point, each theory must be proved, disproved or its limitations clearly stated. It is in this phase that most work is still being accomplished. This examination is important because it provides referents for vigorous outside criticism, the final phase. Calabrese and Baldwin are to be complimented on seeking outside comment. Considerable refinement of the theory has taken place with time.

Effects of low dose X-ray irradiation on purine metabolism in mouse splenocytes.

This study examines the influence of low dose X-ray irradiation on purine nucleotide metabolites such as adenosine, inosine, hypoxanthine, xanthine and uric acid, and hence generation of ATP-mediated energy in mouse splenocytes. It was found that, unlike high dose irradiation which promotes membrane damage, low dose irradiation enhances the ability to regulate the energy metabolisms as reflected by the increase in Na+, K(+)-ATPase activity and the adequate activation of the above salvage pathway. Namely, the levels of adenosine, inosine and uric acid significantly increased, while the levels of xanthine and hypoxanthine decreased significantly. Moreover, the cysteine level and superoxide dismutase activity significantly increased at a dosage of 20 cGy.

[The biological action of physical factors in the critical periods of embryogenesis]. / Biologicheskoe deistvie fizicheskikh faktorov v kriticheskie periody émbriogeneza.

The critical period in a chicken embryonic development (the 10-13-th days of incubation) is revealed under total electromagnetic radiation. This external factor is a physiologically active irritant which can influence functional state of the brain. The increased absorption of electromagnetic energy takes place in this incubation period. Its dynamics within 20 days of embryonic development has phasic, up and down character. Electromagnetic exposure (4 hours a day daily) in the above mentioned period evokes a delay in embryo adaptive motor behavior (biofeedback learning). Morphological investigation shows significant pathological changes--destruction of share brain synapses. The delay in embryo hatching for a day is also detected. Radiation exposure within other periods of incubation (3-6-th or 12-15-th days) was not effective with respect to formation of normal motor pattern in biofeedback experiment.