Red light photobiomodulation rescues murine brain mitochondrial respiration after acute hypobaric hypoxia.

Low-level laser therapy, or photobiomodulation, utilizes red or near-infrared light for the treatment of pathological conditions due to the presence of intracellular photoacceptors, such as mitochondrial cytochrome c oxidase, that serve as intermediates for the therapeutic effects. We present an in-detail analysis of the effect of low-intensity LED red light irradiation on the respiratory chain of brain mitochondria. We tested whether low-level laser therapy at 650 nm could alleviate the brain mitochondrial dysfunction in the model of acute hypobaric hypoxia in mice. The irradiation of the mitochondrial fraction of the left cerebral cortex with low-intensity LED red light rescued Complex I-supported respiration during oxidative phosphorylation, normalized the initial polarization of the inner mitochondrial membrane, but has not shown any significant effect on the activity of Complex IV. In comparison, the postponed effect (in 24 h) of the similar transcranial irradiation following hypoxic exposure led to a less pronounced improvement of the mitochondrial functional state, but normalized respiration related to ATP production and membrane polarization. In contrast, the similar irradiation of the mitochondria isolated from control healthy animals exerted an inhibitory effect on CI-supported respiration. The obtained results provide significant insight that can be beneficial for the development of non-invasive phototherapy.

Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy.

BACKGROUND: Breast cancer neoadjuvant chemotherapy (NACT) allows for assessing tumor sensitivity to systemic treatment, planning adjuvant treatment and follow-up. However, a sufficiently large number of patients fail to achieve the desired level of pathological tumor response while optimal early response assessment methods have not been established now. In our study, we simultaneously assessed the early chemotherapy-induced changes in the tumor volume by ultrasound (US), the tumor oxygenation by diffuse optical spectroscopy imaging (DOSI), and the state of the tumor vascular bed by Doppler US to elaborate the predictive criteria of breast tumor response to treatment. METHODS: A total of 133 patients with a confirmed diagnosis of invasive breast cancer stage II to III admitted to NACT following definitive breast surgery were enrolled, of those 103 were included in the final analysis. Tumor oxygenation by DOSI, tumor volume by US, and tumor vascularization by Doppler US were determined before the first and second cycle of NACT. After NACT completion, patients underwent surgery followed by pathological examination and assessment of the pathological tumor response. On the basis of these, data regression predictive models were created. RESULTS: We observed changes in all three parameters 3 weeks after the start of the treatment. However, a high predictive potential for early assessment of tumor sensitivity to NACT demonstrated only the level of oxygenation, ΔStO2, (ρ = 0.802, p ≤ 0.01). The regression model predicts the tumor response with a high probability of a correct conclusion (89.3%). The "Tumor volume" model and the "Vascularization index" model did not accurately predict the absence of a pathological tumor response to treatment (60.9% and 58.7%, respectively), while predicting a positive response to treatment was relatively better (78.9% and 75.4%, respectively). CONCLUSIONS: Diffuse optical spectroscopy imaging appeared to be a robust tool for early predicting breast cancer response to chemotherapy. It may help identify patients who need additional molecular genetic study of the tumor in order to find the source of resistance to treatment, as well as to correct the treatment regimen.

Late Changes in the Extracellular Matrix of the Bladder after Radiation Therapy for Pelvic Tumors.

Radiation therapy is one of the cardinal approaches in the treatment of malignant tumors of the pelvis. It leads to the development of radiation-induced complications in the normal tissues. Thus, the evaluation of radiation-induced changes in the extracellular matrix of the normal tissue is deemed urgent, since connective tissue stroma degradation plays a crucial role in the development of Grade 3-4 adverse effects (hemorrhage, necrosis, and fistula). Such adverse effects not only drastically reduce the patients' quality of life but can also become life-threatening. The aim of this study is to quantitatively analyze the bladder collagen state in patients who underwent radiation therapy for cervical and endometrial cancer and in patients with chronic bacterial cystitis and compare them to the normal bladder extracellular matrix. MATERIALS AND METHODS: One hundred and five patients with Grade 2-4 of radiation cystitis, 67 patients with bacterial chronic cystitis, and 20 volunteers without bladder pathology were enrolled. Collagen changes were evaluated depending on its hierarchical level: fibrils and fibers level by atomic force microscopy; fibers and bundles level by two-photon microscopy in the second harmonic generation (SHG) mode; general collagen architectonics by cross-polarization optical coherence tomography (CP OCT). RESULTS: The main sign of the radiation-induced damage of collagen fibrils and fibers was the loss of the ordered "basket-weave" packing and a significant increase in the total area of ruptures deeper than 1 µm compared to the intact sample. The numerical analysis of SHG images detected that a decrease in the SHG signal intensity of collagen is correlated with the increase in the grade of radiation cystitis. The OCT signal brightness in cross-polarization images demonstrated a gradual decrease compared to the intact bladder depending on the grade of the adverse event. CONCLUSIONS: The observed correspondence between the extracellular matrix changes at the microscopic level and at the level of the general organ architectonics allows for the consideration of CP OCT as a method of "optical biopsy" in the grading of radiation-induced collagen damage.

Modification in oxidative processes in muscle tissues exposed to laser- and light-emitting diode radiation.

Exposure of living tissues to high-intensity red or near-infrared light can produce the oxidative stress effects both in the target zone and adjacent ones. The protein oxidative modification (POM) products can be used as reliable and early markers of oxidative stress. The contents of modified proteins in the investigated specimens can be evaluated by the 2,4-dinitrophenylhydrazine assay (the DNPH assay). Low-intensity red light is able to decrease the activity of oxidative processes and the DNPH assay data about the POM products in the biological tissues could show both an oxidative stress level and an efficiency of physical agent protection against the oxidative processes. Two control groups of white rats were irradiated by laser light, the first control group by red light and the second one by near-infrared radiation (NIR).Two experimental groups were consequently treated with laser and red low-level light-emitting diode radiation (LED). One of them was exposed to red laser light + LED and the other to NIR + LED. The fifth group was intact. Each group included ten animals. The effect of laser light was studied by methods of protein oxidative modifications. We measured levels of both induced and spontaneous POM products by the DNPH assay. The dramatic increase in levels of POM products in the control group samples when compared with the intact group data as well as the sharp decrease in the POM products in the experimental groups treated with LED low-level light were statistically significant (p ≤ 0.05). Exposure of skeletal muscles to high-intensity red and near-infrared laser light causes oxidative stress that continues not less than 3 days. The method of measurement of POM product contents by the DNPH assay is a reliable test of an oxidative process rate. Red low-intensity LED radiation can provide rehabilitation of skeletal muscle tissues treated with high-intensity laser light.

Low-power light and isolated rat hearts after ischemia of myocardium.

We studied the influence of low-intensity red light on restoration of isolated heart contractility, on lipid peroxidation processes and a state of the superoxide dismutase (SOD) activity in myocardial tissues of isolated hearts. It was found that after ischemia modeled and perfusion restored the light illumination results in acceleration of myocardial contractility recovery, rising of the SOD activity and reduction in the amount of molecular products of lipid peroxidation.