External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DNA double-strand breaks (DSBs) activate the ATM/CHEK2/p53 pathway, inducing the transcription of stress genes. The dynamic nature of this transcriptional response has not been directly observed in vivo in humans. In this study we monitored the messenger RNA transcript abundances of nine DNA damage-responsive genes (CDKN1A, GADD45, CCNG1, FDXR, DDB2, MDM2, PHPT1, SESN1, and PUMA), eight of them regulated by p53 in circulating blood leukocytes at different time points (2, 6–8, 16–18, and 24 h) in cancer patients (lung, neck, brain, and pelvis) undergoing radiotherapy. We discovered that, although the calculated mean physical dose to the blood was very low (0.038–0.169 Gy), an upregulation of Ferredoxin reductase (FDXR) gene transcription was detectable 2 h after exposure and was dose dependent from the lowest irradiated percentage of the body (3.5% whole brain) to the highest, (up to 19.4%, pelvic zone) reaching a peak at 6–8 h. The radiation response of the other genes was not strong enough after such low doses to provide meaningful information. Following multiple fractions, the expression level increased further and was still significantly up-regulated by the end of the treatment. Moreover, we compared FDXR transcriptional responses to ionizing radiation (IR) in vivo with healthy donors’ blood cells exposed ex vivo and found a good correlation in the kinetics of expression from the 8-hours time-point onward, suggesting that a molecular transcriptional regulation mechanism yet to be identified is involved. To conclude, we provided the first in vivo human report of IR-induced gene transcription temporal response of a panel of p53-dependant genes. FDXR was demonstrated to be the most responsive gene, able to reliably inform on the low doses following partial body irradiation of the patients, and providing an expression pattern corresponding to the % of body exposed. An extended study would provide individual biological dosimetry information and may reveal inter-individual variability to predict radiotherapy-associated adverse health outcomes.
Background. Diabetes mellitus affects almost all body systems, but the most dramatic complications occur in the lower extremities. Diabetic foot syndrome takes the leading position in the list of complications of diabetes mellitus, leading to early disability and mortality. At present, a new technology - photodynamic therapy is being intensively developed worldwide. This technique can be used in many different fields of medicine, including purulent surgery. This study aimed to investigate the possibility of using 5-aminolevulinic acid as an photosensitizer in photodynamic therapy in the complex treatment of chronic wounds in patients with ischemic and mixed forms of diabetic foot syndrome. Materials and Methods. In 2021, 10 patients with type 2 diabetes mellitus and ischemic and mixed forms of diabetic foot syndrome of both sexes, aged 52 to 75 years, were observed. As a preparation for photodynamic therapy, daily dressings with hydrogel were applied (3-5 days). During this period, limb revascularization was performed, the aim of which was to restore the blood flow to the foot, preferably through the anterior or posterior tibial artery. After the restoration of the main blood flow, photodynamic therapy was performed: after sanitation of the wound surface with physiological NaCl solution, Levuderm gel (6% gel phosphate of 5-aminolaevulinic acid) was applied and covered with occlusive dressing for 2 hours, after which the gel remains were removed and irradiation with Korobov photonic matrices "Barva Flex" with 660 nm wave length was carried out. Energy applied to the wound averaged 30-40 J/cm2. The light power density was between 0.1-1.0 W/cm2, and the exposure time varied according to the wound area. Results. After photodynamic therapy on days 2-3, perifocal oedema decreased. By days 5-7, the quality of granulation and the degree of wound epithelialization significantly improved. The wound healing rate on days5-7 of treatment was 1,58±0,44, and on days 10-12 - 4,72±0,63 (p <0,01). The evaluation of the wound healing rate showed good and satisfactory results: By day 32, the wound in the study group was completely epithelialized in the majority of patients (88.9%). Conclusions. The method we have developed for treating chronic wounds using photodynamic therapy is pathogenetically feasible and highly effective compared to conventional therapies. Combined light exposure using photosensitizer stimulates the formation of reactive oxygen species, increasing the effect of phagocytic cells, which is manifested in the activation of neutrophil chemotaxis, adhesion, and endocytosis. photodynamic therapy using aminolaevulinic acid as a photosensitizer, enhances molecular mechanisms of intercellular interaction at all stages of primary immunity activation.
Objective. Elaboration of complex approach to treatment of trophic ulcers of venous etiology, using photodynamical tissue therapy and modern types of the wound coverage. Materials and methods. Into the investigation 24 patients were included, suffering venous ulcers on background of postthrombophlebitic disease and ageing from 31 to 79 yrs old. Into the comparison group there were included 14 patients, in whom a standard treatment (venotonic preparations, elastic compression, local application of multicomponent ointments depending on the wound phase present) was used. Into the main group10 patients were included, in whom the elaborated procedure of photodynamical therapy was applied. In treatment of the patients the Korobov’s photonic matrix «Barva Flex», owing spectral diapason 700-630 nm, corresponding to red light, was applied. Gel «Levuderm» (6% gel 5-aminolevulinic acid phosphate, which constitutes a natural predecessor of endogenous photosensitizer protoporphyrin IX) was applied. Results. Transition of the wound process to the second stage in the comparison group was durable, in 50% of patients epithelization did not complete up to 45th day of treatment. In the main group, under the impact of the treatment method proposed, the term of granulations appearance have had shortened as well as filling in of the wound by mature granulation tissue, and epithelization have accelerated by 29.8%, comparing with standard therapy. Conclusion. This investigation owes a shortage because of insufficient volume of sampling. Thus, it is necessary to perform further controlled investigations to discover the mechanisms of basic impact of the 5-aminolevulinic acid photodynamical therapy on the wound healing process.
Phosphorescence is considered one of the non-invasive glioblastoma testing methods based on studying molecular energy and the metabolism of L-tryptophan (Trp) through KP, which provides essential information on regulating immunity and neuronal function. This study aimed to conduct a feasibility study using phosphorescence in clinical oncology as an early prognostic test in detecting Glioblastoma. Materials and Methods. This study was conducted on 1039 patients who were operated on with follow-up between January 1, 2014, and December 1, 2022, and retrospectively evaluated in participating institutions in Ukraine (the Department of Oncology, Radiation Therapy, Oncosurgery, and Palliative Care at the Kharkiv National Medical University). Method of protein phosphorescence detection included two steps. During the first step, of luminol-dependent phosphorescence intensity in serum was carried out after its activation by the light source, according to the spectrofluorimeter method, as follows. At a temperature of 30oC, serum drops were dried for 20 minutes to form a solid film. After that, we put the quartz plate with dried serum in a phosphoroscope of luminescent complex and measured the intensity. With the help of Max-Flux Diffraction Optic Parallel Beam Graded Multilayer Monochromator (Rigaku Americas Corporation) following spectral lines as 297, 313, 334, 365, 404, and 434 nm were distinguished and absorbed by serum film in the form of light quantum. The monochromator exit split width was 0.5 mm. Results and conclusion. Considering the limitations of each of the non-invasive tools currently available, phosphorescence-based diagnostic methods are ideally integrated into the NIGT platform: a non-invasive approach for visualizing a tumor and its main tumor characteristics in the spatial and temporal order. Because trp is present in virtually every cell in the body, these fluorescent and phosphorescent fingerprints can be used to detect cancer in many different organs. Using phosphorescence, it is possible to create predictive models for GBM in both primary and secondary diagnostics. This will assist clinicians in selecting the appropriate treatment option, monitoring treatment, and adapting to the era of patient-centered precision medicine.
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