Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice

Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db−/db− mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α-smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes

Oncolytic Sendai Virus Therapy of Canine Mast Cell Tumors (A Pilot Study)

Background: Canine mastocytomas (mast cell tumors) represent a common malignancy among many dog breeds. A typical treatment strategy for canine mastocytomas includes surgery, chemo- and radio-therapy, although in many cases the therapy fails and the disease progression resumes. New treatment approaches are needed.Aims: The goal of this pilot study was to examine safety and efficacy of oncolytic Sendai virus therapy administered to canine patients with cutaneous or subcutaneous mastocytomas.Materials and Methods: Six canine patients, with variable grades and stages of the disease, received virus therapy, either as a monotherapy, or in combination with surgery. The therapy included two or more virus applications administered weekly or biweekly. Each application of Sendai virus (107-108.6 EID50) consisted of multiple individual 0.01–0.1 ml injections delivered intratumorally, intradermally around a tumor, and under a tumor bed.Results: The treatment was well tolerated, with minor transitory side effects. Of the six dogs, two did not receive surgery or any other treatment besides the virus injections. The other four animals underwent radical or debulking surgeries, and in three of them the subsequent administration of Sendai virus completely cleared locally recurrent or/and remaining tumor masses. Five dogs demonstrated a complete response to the treatment, the animals remained disease free during the time of observation (2–3 years). One dog responded only partially to the virotherapy; its after-surgical recurrent tumor and some, but not all, metastases were cleared. This dog had the most advanced stage of the disease with multiple enlarged lymph nodes and cutaneous metastases.Conclusion: The results of the pilot study suggest that Sendai virus injections could be safe and efficient for the treatment of dogs affected by mastocytomas.They also suggest the need of further studies for finding optimal schemes and schedules for this kind of therapy

Influence of Heat Stress and Water Availability on Productivity of Silage Maize (<i>Zea mays</i> L.) under Different Tillage and Fertilizer Management Practices in Rostov Region of Russia

The aridization of the climate negatively affects the growth and development of plants and their productivity. The aim of this study was to determine the effect of heat stress and water availability on maize for silage under aridization and to find out the effectiveness of technological methods to maximize the use of available moisture. A long-term multifactorial experiment was performed during the period 1991–2020 in the region south of Rostov, Russia. The long-term multifactorial experiment is located in a zone of high heat supply and insufficient moisture, so the latter factor limits the yield of corn and dictates the need to find solutions to increase its environmental sustainability in extreme weather conditions. The values of the hydrothermal coefficient (HTC) were determined for the period of maize cultivation for each year of the study, ranked in ascending order and grouped into clusters. The results were mathematically processed by calculating the mean values (M) and their standard deviations (±SEM) with Statistica 13.3 software. The optimum conditions for silage maize development were found under the combination of 265 mm of rainfall and a 19.8 °C average temperature during the growing season. The maximum yield of silage maize was 33.8–45.2 t ha−1. In dry years (HTC = 0.3), tillage had an advantage: the yield increase was 0.2–1.6 t ha−1. In wet years, moldboard tillage was preferable: the yield increase was 0.3–2.9 t ha−1. The application of farmyard manure for fertilization increased the yield by 10.5–41.9%. Increasing the fertilizer rate by 1.5 times increased the yield by 21.0–59.8%. In drought, tillage and average fertilizer rate provided returns by increasing yields up to 7.7 kg/kg. Our study provides valuable recommendations in fodder production, promotes moisture conservation, preserves soil fertility on the slopes when cultivating corn for silage, and will be useful to specialists in improving the efficiency of agricultural production

Distribution, phosphorylation, and activities of Hsp25 in heat-stressed H9c2 myoblasts: a functional link to cytoprotection

The behavior of the endogenous heat shock protein 25 (Hsp25) in heat-stressed rat H9c2 myoblasts was studied. After mild or severe heating, this protein became less extractable with Triton X-100 and displayed characteristic immunofluorescence patterns, namely (1) granules in the nucleus, and (2) association with F-actin bundles in the cytoplasm. The intranuclear granulation of Hsp25 and its association with F-actin were sensitive to drugs affecting Hsp25 phosphorylation (cantharidin, sodium orthovanadate, SB203580, SB202190). Isoform analysis of Hsp25 translocated to the nucleus-free cytoskeletal fraction revealed only mono- and biphosphorylated Hsp25 and no unphosphorylated Hsp25. Transfected luciferase with initial localization in the nucleosol became colocalized with the Hsp25-containing granules after a heat shock treatment that denatured the enzyme in the cells. The association of Hsp25 with actin filaments after a mild heat stress conferred protection from subsequent F-actin–damaging treatments with cytochalasins (D and B) or severe heat stress. We hypothesize that (1) the binding of heat-denatured nucleosolic proteins to the Hsp25 contained in specific granular structures may serve for the subsequent chaperoning or degradation of the bound proteins, and (2) the actin cytoskeleton is stabilized by the direct targeting of phosphorylated Hsp25 to microfilament bundles