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Tumor-associated fibrosis contributes to an immunosuppressive microenvironment that hinders effective anti-tumor immune responses. This study investigates the potential of IOA-289, a novel autotaxin (ATX) inhibitor, which blocks lysophosphatidate (LPA) production and signaling, in modulating fibrosis in breast tumors. Bioinformatic analysis of human breast tumors revealed a strong correlation between levels of LPA1,-4 receptors and extracellular matrix (ECM) genes. Interaction of ECM molecules and integrin β1/CD44 between myofibroblasts and other cell types had the highest contribution to cell-cell communication. We showed that LPA induced α-smooth muscle actin mRNA in mouse mammary fibroblasts and increased expressions of collagen type-I α1 chain (COL1A1) and lamininγ1. IOA-289 decreased the expressions of COL1A1, fibronectin-1, and transforming growth factor β1 (TGFβ1) in E0771 breast tumors in mice. Masson's trichrome staining revealed a marked decrease in collagen deposition within breast tumors of IOA-289-treated mice. Decreased tumor fibrosis aligns with previous findings that IOA-289 enhanced the infiltration of CD8+ cytotoxic T cells and decreased fibrotic factors including leukemia inhibitory factor and transforming growth factor-beta1 in tumors. We also demonstrated that E0771 cells express negligible ATX and LPA receptors. Therefore, ATX inhibition did not affect cancer cells directly in our model. These results underscore the potential of ATX inhibitors in reprogramming the tumor microenvironment to favor anti-tumor immunity and attenuate fibrosis. ATX inhibitors are in clinical trials for treating idiopathic pulmonary fibrosis and pancreatic cancer. Our results support the development of ATX inhibitors as a strategy for improving the treatment of breast cancer and other diseases involving fibrosis.
The article is devoted to the study of the conservation of biological diversity in the forest ecosystems of the Vologda region. The paper considers the main stages of identifying key biotopes and valuable trees in the process of logging, confirmed by the practical experience of enterprises in the Vologda region.
Abstract The utilization of natural ventilation to reduce thermal load and enhance thermal comfort in buildings is on the rise. Furthermore, in light of the COVID‐19 impact, natural ventilation is gaining prominence as an increasingly vital technology. However, it is crucial to address potential challenges associated with natural ventilation, particularly its impact on the indoor thermal environment. This study aimed to examine and offer insights into natural ventilation design and operational strategies for office buildings. We initially summarized the criteria and effective opening area of natural ventilation openings (αAi) in Japanese naturally ventilated buildings. Among the 37 investigated office buildings, we found a positive correlation between the natural ventilation room area and the αAi. Approximately, 25 buildings maintained a ratio of αAi to the natural ventilation room area ranging from 0.1%–0.5%. Additionally, we conducted measurements of the indoor thermal environment, focusing on the opening ratio of natural ventilation openings. The difference of indoor and outdoor temperature showed a strong negative correlation with the opening ratio, while wind direction and global solar radiation exhibited significant correlations as well. These research findings provide valuable insights for future natural ventilation designs and the incorporation of opening ratio concepts into operational methods.
The article discusses the results of studies in mature and overmature pine, larch and spruce forests of the green moss group of forest types (more than 80), passed through renewal felling in the north-taiga forest region of the European part of the Russian Federation. The results of the research were obtained on the basis of observation materials in the period from 1999-2022. Works were carried out to study the felling parameters to assess the forest plantations passed through the renewal felling: forest type, soil conditions, age, tree stand structure, composition and age, availability of seed sources, presence of undergrowth and young generation of economically valuable species, as well as changes in taxation indicators. It is advisable to carry out renewal cuttings in mature and overmature stands, thereby catching up with natural decay in order to create the necessary conditions for good growth and formation of a forest stand. One of the options may be the creation of forest plantations of such a composition, density, which could provide the best performance in terms of the main quantitative and qualitative characteristics.
В основе статьи обобщение многолетних исследований в области селекции и семеноводства в таежной зоне Европейского севера России исходя из актуальности задач по реализации Стратегии развития лесного комплекса Российской Федерации до 2030 г.Представлена интенсивная технология ускоренного производства хвойных лесов.Показаны технологические возможности создания лесосеменных плантаций на селекционной основе в северных лесах.Приведен комплекс селекционно ценных признаков, позволяющих на ранней стадии развития проводить отбор сосны -число семядолей, треххвойность, угол ветвления кроны
