Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes erosion of articular cartilage and bone and has adverse effects on both patients and livestock animals. The aim of the present study was to investigate the role of interleukin-1β (IL-1β) in the pathogenesis of RA, and to further determine whether injection of IL-1β small interfering RNA (siRNA) or transplantation of IL-1β siRNA + bone marrow mesenchymal stem cells (BMSCs) can ameliorate RA in rats. A collagen-induced arthritis (CIA) rat model was established by injecting type II collagen for 4 weeks. Next, CIA rats were randomly divided into three groups and injected or transplanted with PBS, IL-1β siRNA and IL-1β siRNA + BMSCs for another 4 weeks. The CIA rat model was successfully established, as demonstrated by the higher toe swelling value, thymus and spleen/body weight, immobility time and serum IL-1β concentration, as well as lower body weight, climbing time and mRNA expression of programmed death-1 (PD-1), transforming growth factor-β1 (TGF-β1) and forkhead box protein 3 (Foxp3) in the spleen, compared with control rats. Furthermore, histopathology results demonstrated that joint swelling and redness were observed in the knee joints of CIA rats. H&E results revealed that CIA rats presented erosive destruction of the bone and ulceration of the articular cartilage. In addition, in vitro results demonstrated that IL-1β expression was successfully silenced after IL-1β siRNA transfection in lipopolysaccharide-stimulated BMSCs. When compared with the results of PBS rats, both IL-1β siRNA injection and IL-1β siRNA + BMSC transplantation significantly increased the body weight, climbing time and mRNA expression of PD-1, TGF-β1 and Foxp3 in the spleen, while significantly reduced the immobility time and serum IL-1β concentration. In addition, when compared with that of IL-1β siRNA injection, IL-1β siRNA + BMSC transplantation exhibited markedly higher therapeutic efficacy against CIA. These results demonstrated that higher IL-1β contributed to the pathogenesis of CIA, and that IL-1β siRNA injection ameliorated CIA, while its combination with BMSCs exerted synergistic effects, which may be beneficial against RA.
The emergence, in recent decades, of an entirely new area of “Mitochondrial dynamics”, which consists principally of fission and fusion, reflects the recognition that mitochondria play a significant role in human tumorigenesis and response to therapeutics. Proteins that determine mitochondrial dynamics are referred to as “shaping proteins”. Marked heterogeneity has been observed in the response of tumor cells to chemotherapy, which is associated with imbalances in mitochondrial dynamics and function leading to adaptive and acquired resistance to chemotherapeutic agents. Therefore, targeting mitochondria-shaping proteins may prove to be a promising approach to treat chemotherapy resistant cancers. In this review, we summarize the alterations of mitochondrial dynamics in chemotherapeutic processing and the antitumor mechanisms by which chemotherapy drugs synergize with mitochondria-shaping proteins. These might shed light on new biomarkers for better prediction of cancer chemosensitivity and contribute to the exploitation of potent therapeutic strategies for the clinical treatment of cancers.
Natural disasters, including collapse, landslides, and debris flows, commonly occur in the Yili River Valley as a result of its distinctive terrain and climate. A large proportion of these are loess landslides. Hence, studying the mechanism of their occurrence is crucial. The loess in the Yili River Valley has a high mica content. By using freeze-thaw (FT) cycling tests, unconsolidated and undrained triaxial shear tests, and FT cycling experiments, the study clarifies the impact of mica content on the mechanical properties of the loess in the Yili River Valley under FT cycling conditions. The findings demonstrated that the loess’s shear strength was negatively impacted by both the mica content and freeze-thaw cycles (FTCs). Under the same FT cycle conditions, the shear strength of the Yili Valley loess decreased with an increase in the mica content, particularly during the first ten cycles. Cohesion represented the impact of the mica content on the shear strength parameters. The cohesion decreases as the mica content increases. After ten cycles, the values of the cohesion tended to become stable, while the internal friction angle showed the opposite trend. For the same mica content, the shear strength of the Yili valley loess decreased with the increase in the number of FTCs, while the cohesion decreased, and the internal friction angle first increased and then decreased. The study’s findings might offer a theoretical foundation for preventing and reducing loess landslides in the Yili River Valley caused by FTCs and high mica content.
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