Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model.</p> <p>Results</p> <p>Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord.</p> <p>Conclusions</p> <p>These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.</p

ERK in Learning and Memory: A Review of Recent Research

The extracellular signal-regulated kinase (ERK) pathway is a member of the mitogen-activated protein kinase (MAPK) superfamily, which is an important, highly conserved family of enzymes associated with cell membrane receptors and regulative targets. In the central nervous system, there is almost no mature neuronal proliferation and differentiation, but the regulation of MAPK and its upstream and downstream molecular pathways is still widespread, with the ERK signaling pathway being one of the most actively studied signal transduction pathways. It is activated by a variety of cell growth factors and substances which promote mitotic activity, and transmits extracellular signals from the cell surface to the nucleus, which transmission plays an important role in the process of cell proliferation and differentiation. In recent years, accumulating evidence has shown that the ERK signaling pathway has an important link with the higher functions of learning and memory

Molecular mechanism underlying miR-204-5p regulation of adipose-derived stem cells differentiation into cells from three germ layers

Abstract The limited differentiation ability of adipose-derived stem cells (ADSCs) limits their application in stem cell therapy and regenerative medicine. Here, we explore the molecular mechanism by which miR-204-5p regulates ADSCs differentiation into cells derived from the three germ layers (i.e., adipocytes, neurocytes, and hepatocytes). Although miR-204-5p overexpression inhibited ADSCs differentiation into adipocytes, neurocyte and hepatocyte differentiation were promoted. Mechanistically, miR-204-5p inhibited the expression of PPARG by regulating the AMPK signaling pathway, thereby inhibiting ADSCs differentiation into adipocytes. Further, miR-204-5p regulated JAG1/NOTCH3 axis for the inhibition of differentiation into adipocytes and promotion of differentiation into neurocytes. miR-204-5p might also promote ADSCs differentiation into hepatocytes by upregulating E2F8. The findings of this study provide novel insights into the regulatory mechanisms underlying early embryonic development and will help to facilitate the application of ADSCs in stem cell therapy and regenerative medicine

Low-temperature CO oxidation over integrated penthorum chinense-like MnCo2O4 arrays anchored on three-dimensional Ni foam with enhanced moisture resistance

Advanced integrated nanoarray (NA) catalysts have been designed by growing metal-doped Co3O4 arrays on nickel foam with robust adhesion. Ternary MCo2O4 NA catalysts were prepared by doping urchin-like Co3O4 with different transition metals (Cu2+, Mn2+, Fe2+, Ni2+, Zn2+, Fe3+ and Al3+). These catalysts exhibited novel morphologies and can be directly applied as monolithic materials for CO oxidation. Among the MCo2O4 NA catalysts, CuCo2O4 nanoneedles manifested the highest catalytic activity in dry air, achieving an efficient 100% CO oxidation conversion of 20000 h(-1) at 146 degrees C, due to its reducibility at lower temperature, lattice distortion of the spinel structure, and abundant surface-adsorbed oxygen (O-ads). The doped catalytic systems were further optimized by controlling the volume ratio of reactive components in the mixed solvent, the Cu or Mn contents to determine excellent catalysts for direct application to CO oxidation at 1.0 vol% moisture. Penthorum chinense-like MnCo2O4 NAs showed optimal catalytic performance at 1 vol% moisture (T-100 = 175 degrees C), with activity higher than that of the CuCo2O4 NA catalyst, indicating that the synergistic effect between MnOx and Co3O4 improved the moisture resistance and stability. It was concluded that the moisture resistance provided by introducing active sites on Co-based catalysts decreased as follows: Mn sites &gt; Co sites &gt; Cu sites &gt; Ni sites. MCo2O4 NAs, with predominantly exposed {110} surfaces, showed higher catalytic activity than catalysts with exposed {111} surfaces. This study suggests that the as-prepared MnCo2O4 NAs anchored on 3D Ni foam with remarkable moisture resistance have potential applications in CO oxidation.</p