Effect of Photobiomodulation on Vinblastine-Poisoned Murine HERS Cells

Objective: The aim of this study was to investigate the effect of near-infrared (NIR) photobiomodulation on the proliferation and glutathione levels in murine Hertwig\u27s epithelial root sheath (HERS) cells after poisoning with vinblastine. Background: Photobiomodulation has been shown to improve wound healing in a number of animal models. There have been no studies on the effect of photobiomodulation on cancer-related chemotherapy injury to the cells that initiate tooth root growth. Materials and Methods: Control groups consisted of murine HERS cells without vinblastine (VB−) and cells with vinblastine at 10, 20, and 30 ng/mL (VB10, VB20, and VB30). Experimental groups consisted of these same groups with light therapy (VB-L, VB10L, VB20L, and VB30L). The cells were exposed to vinblastine for 1 h. Photobiomodulation consisted of a 75-cm2 gallium-aluminum-arsenide light-emitting diode (LED) array at an energy density of 12.8 J/cm2, delivered with 50 mW/cm2 power over 256 s. Results: Vinblastine alone significantly decreased HERS cell proliferation and glutathione levels at all concentrations (VB10 [−55%, p \u3c 1.0 × 10−8]; VB20 [−72%, p \u3c 1.0 × 10−9]; VB30 [−80%, p \u3c 1.0 × 10−10]; and VB10 [−36%, p \u3c 0.0001]; VB20 [−49%, p \u3c 1.0 × 10−6]; VB30 [−53%, p \u3c 1.0 × 10−7] respectively). Photobiomodulation significantly increased cell proliferation at all levels of vinblastine exposure (VB10L [+50%, p \u3c 0.0001]; VB20L [+45%, p \u3c 0.05]; VB30 [+39%, p \u3c 0.05]) but not of the control (+22%, p  = 0.063). The photobiomodulation significantly increased glutathione production in all concentrations of vinblastine except 20 ng/mL (VB10L [+39%, p = 0.007]; VB20L [+19%, p = 0.087]; VB30 [+14%, p = 0.025]) and the control (+12%, p = 0.13). Conclusions: Photobiomodulation demonstrated an improvement in proliferation and glutathione levels in vinblastine-poisoned murine HERS cells

KATP Channel Openers Have Opposite Effects on Mitochondrial Respiration Under Different Energetic Conditions

Mitochondrial (m) KATP channel opening has been implicated in triggering cardiac preconditioning. Its consequence on mitochondrial respiration, however, remains unclear. We investigated the effects of two different KATP channel openers and antagonists on mitochondrial respiration under two different energetic conditions. Oxygen consumption was measured for complex I (pyruvate/malate) or complex II (succinate with rotenone) substrates in mitochondria from fresh guinea pig hearts. One of two mKATP channel openers, pinacidil or diazoxide, was given before adenosine diphosphate in the absence or presence of an mKATP channel antagonist, glibenclamide or 5-hydroxydecanoate. Without ATP synthase inhibition, both mKATP channel openers differentially attenuated mitochondrial respiration. Neither mKATP channel antagonist abolished these effects. When ATP synthase was inhibited by oligomycin to decrease [ATP], both mKATP channel openers accelerated respiration for both substrate groups. This was abolished by mKATP channel blockade. Thus, under energetically more physiological conditions, the main effect of mKATP channel openers on mitochondrial respiration is differential inhibition independent of mKATP channel opening. In contrast, under energetically less physiological conditions, mKATP channel opening can be evidenced by accelerated respiration and blockade by antagonists. Therefore, the effects of mKATP channel openers on mitochondrial function likely depend on the experimental conditions and the cell\u27s underlying energetic state

Clinical and Experimental Applications of NIR-LED Photobiomodulation

This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as “photobiomodulation,” uses light in the far-red to near-infrared region of the spectrum (630–1000 nm) and modulates numerous cellular functions. Positive effects of NIR–light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

Prenatal muscle development in a mouse model for the secondary dystroglycanopathies

The defective glycosylation of α-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-related protein (FKRP) are one of the most common causes of secondary dystroglycanopathy in the UK and are associated with a wide spectrum of disease. Whilst central nervous system involvement has a prenatal onset, no studies have addressed prenatal muscle development in any of the mouse models for this group of diseases. In view of the pivotal role of α-dystroglycan in early basement membrane formation, we sought to determine if the muscle formation was altered in a mouse model of FKRP-related dystrophy

TESS Discovery of an ultra-short-period planet around the nearby M dwarf LHS 3844

Data from the newly-commissioned \textit{Transiting Exoplanet Survey Satellite} (TESS) has revealed a "hot Earth" around LHS 3844, an M dwarf located 15 pc away. The planet has a radius of $1.32\pm 0.02$ $R_\oplus$ and orbits the star every 11 hours. Although the existence of an atmosphere around such a strongly irradiated planet is questionable, the star is bright enough ($I=11.9$, $K=9.1$) for this possibility to be investigated with transit and occultation spectroscopy. The star's brightness and the planet's short period will also facilitate the measurement of the planet's mass through Doppler spectroscopy.Comment: 10 pages, 4 figures. Submitted to ApJ Letters. This letter makes use of the TESS Alert data, which is currently in a beta test phase, using data from the pipelines at the TESS Science Office and at the TESS Science Processing Operations Cente