Fumarate mitigates disruption induced by fenpropathrin in the silkworm Bombyx mori (Lepidoptera): A metabolomics study.

The silkworm Bombyx mori L. is a model organism of the order Lepidoptera. Understanding the mechanism of pesticide resistance in silkworms is valuable for Lepidopteran pest control. In this study, comparative metabolomics was used to analyze the metabolites of 2 silkworm strains with different pesticide resistance levels at 6, 12, and 24 h after feeding with fenpropathrin. Twenty-six of 27 metabolites showed significant differences after fenpropathrin treatment and were classified into 6 metabolic pathways: glycerophospholipid metabolism, sulfur metabolism, glycolysis, amino acid metabolism, the urea cycle, and the tricarboxylic acid (TCA) cycle. After analyzing the percentage changes in the metabolic pathways at the 3 time points, sulfur metabolism, glycolysis, and the TCA cycle showed significant responses to fenpropathrin. Confirmatory experiments were performed by feeding silkworms with key metabolites of the 3 pathways. The combination of iron(II) fumarate + folic acid (IF-FA) enhanced fenpropathrin resistance in silkworms 6.38 fold, indicating that the TCA cycle is the core pathway associated with resistance. Furthermore, the disruption of several energy-related metabolic pathways caused by fenpropathrin was shown to be recovered by IF-FA in vitro. Therefore, IF-FA may have a role in boosting silkworm pesticide resistance by modulating the equilibrium between the TCA cycle and its related metabolic pathways.

Excessive mechanical stretch­mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/ß­catenin signaling pathway.

Excessive biomechanical loading is considered an important cause of osteoarthritis. Although the mechanical responses of chondrocytes and osteoblasts have been investigated, their communication during mechanical loading and the underlying molecular mechanisms are not yet fully known. The present study investigated the effects of excessive mechanically stretched osteoblasts on the metabolism and apoptosis of chondrocytes, and also assessed the involvement of the Wnt/ß­catenin signaling pathway. In the present study, rat chondrocytes and osteoblasts were subjected to mechanical tensile strain, and an indirect chondrocyte­osteoblast co­culture model was established. Reverse transcription­quantitative PCR and western blotting were performed to determine the expression levels of genes and proteins of interest. An ELISA was performed to investigate the levels of cytokines, including matrix metalloproteinase (MMP) 13, MMP 3, interleukin­6 (IL­6) and prostaglandin E2 (PG E2), released from osteoblasts. Flow cytometry was performed to detect the apoptosis of chondrocytes exposed to stretched osteoblast conditioned culture medium. The levels of MMP 13, IL­6 and PG E2 increased significantly in the supernatants of stretched osteoblasts compared with the un­stretched group. By contrast, the mRNA expression levels of Collagen 1a and alkaline phosphatase were significantly decreased in osteoblasts subjected to mechanical stretch compared with the un­stretched group. The mRNA expression level of Collagen 2a was significantly decreased, whereas the expression levels of MMP 13 and a disintegrin and metalloproteinase with thrombospondin­like motifs 5 were significantly increased in chondrocytes subjected to mechanical stretch compared with the un­stretched group. In the co­culture model, the results indicated that excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes, which was partly inhibited by Wnt inhibitor XAV­939. The results of the present study demonstrated that excessive mechanical stretch led to chondrocyte degradation and inhibited osteoblast osteogenic differentiation; furthermore, excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes via the Wnt/ß­catenin signaling pathway.

[Effects of pulsed magnetic field on insulin-like growth factor-1 (IGF-1) in cerebrospinal fluid and effects of IGF-1 on functional recovery].

OBJECTIVE: To study the effects of pulsed magnetic field on insulin-like growth factor-1 (IGF-1) level in the cerebrospinal fluid (CSF) and the association of IGF-1 alterations with the activities of daily living (ADL) of patients with brain injury. METHODS: Sixty-five patients with brain injury were divided randomly into the control group (n=30) and magnetic therapy group (n=35), both receiving conventional therapy and in the latter group, daily pulsed magnetic field treatment (20-40 mT, 50 Hz, 20 min per time, 1 time per day) for 14 consecutive days were administered. On the first and 14th days of the treatment, 2 ml CSF was collected from the cases patients for IGF-1 measurement by radioimmunoassay, and Barthel index (BI) was used to assess the ADL of the patients. RESULTS: After a 14-day treatment, IGF-1 level in the CSF were significantly increased in the magnetic group in comparison with the level before the treatment and with those in the control group (P<0.05). IGF-1 in the CSF underwent no significant changes in the control group (P>0.05). The scores of BI increased significantly in both groups after the treatment (P<0.01), but the increment was more obvious in the magnetic therapy group (P<0.05). A significant positive correlation was found between IGF-1 level in the CSF and BI in these patients (r=0.283, P=0.022). CONCLUSION: Pulsed magnetic field might increase IGF-1 level in the CSF of patients with brain injury to promote the recovery of the patients ADL, suggesting its potential clinical value in the treatment of brain injury.