An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration.

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.

Gallic acid induces the apoptosis of human osteosarcoma cells in vitro and in vivo via the regulation of mitogen-activated protein kinase pathways.

To examine the antitumor effects of gallic acid (GA) on osteosarcoma, two human osteosarcoma cell lines U-2OS and MNNG/HOS were treated by GA and subjected to cell proliferation and apoptosis assays. In addition, MNNG/HOS xenograft tumors were established in nude BALB/c mice to evaluate the anticancer capacity of GA in vivo. The results showed that GA inhibited the proliferation and induced the apoptosis of osteosarcoma cells, accompanied by the upregulation of p-38 activation and the downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK1/2) activation. Additionally, p38 MAPK inhibitor abrogated GA-induced growth inhibition of osteosarcoma cells, whereas JNK or ERK1/2 inhibitors sensitized osteosarcoma cells to GA-induced growth inhibition. In vivo studies further showed that GA administration decreased xenograft tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of PCNA and CD31 expression and upregulation of apoptosis in MNNG/HOS tumor tissues following GA treatment. This study demonstrates the antitumor efficacy of GA for osteosarcoma that is mediated by the modulation of cell proliferation, apoptosis, and angiogenesis. Our findings suggest that GA could be a potent agent for osteosarcoma intervention.

The relationship between low pH in intervertebral discs and low back pain: a systematic review.

INTRODUCTION: To systematically review the relationship between low pH in intervertebral discs and low back pain. MATERIAL AND METHODS: Electronic database (PubMed, ISI Web of Science, Cochrane Library, CINAHL, AMED, and China National Knowledge Infrastructure) searches and hand searching of conference proceedings were conducted. Two authors independently evaluated the methodological quality and abstracted relevant data according to standard criteria. Then the experimental methods and samples employed in the finally retrieved articles were assessed. RESULTS: We first retrieved 136 articles regarding pain and pH, and only 16 of them were mainly about low back pain and pH. Finally, 7 articles met our expectation to focus on the pathogenesis of low back pain caused by pH. In these 7 studies the authors held three opinions to explain the pathogenesis of low back pain in relation to low pH. First, low pH caused by lactate stimulates the muscle and increases the muscle tension, which causes low back pain. Second, low pH stimulates the nerve roots and produces the feeling of pain. Third, low pH changes the matrix metabolism, leading to neuronal death and low back pain. CONCLUSIONS: In this systematic review we propose a new hypothesis that low back pain may be caused by low pH based on the previous literature. Further experimental studies are necessary to verify our hypothesis. This hypothesis will promote our understanding of the pathogenesis of low back pain and the development of novel diagnostic and therapeutic approaches for low back pain.

Analysis of the statistical thermodynamic model for nonlinear binary protein adsorption equilibria.

The statistical thermodynamic (ST) model was used to study nonlinear binary protein adsorption equilibria on an anion exchanger. Single-component and binary protein adsorption isotherms of bovine hemoglobin (Hb) and bovine serum albumin (BSA) on DEAE Spherodex M were determined by batch adsorption experiments in 10 mM Tris-HCl buffer containing a specific NaCl concentration (0.05, 0.10, and 0.15 M) at pH 7.40. The ST model was found to depict the effect of ionic strength on the single-component equilibria well, with model parameters depending on ionic strength. Moreover, the ST model gave acceptable fitting to the binary adsorption data with the fitted single-component model parameters, leading to the estimation of the binary ST model parameter. The effects of ionic strength on the model parameters are reasonably interpreted by the electrostatic and thermodynamic theories. The effective charge of protein in adsorption phase can be separately calculated from the two categories of the model parameters, and the values obtained from the two methods are consistent. The results demonstrate the utility of the ST model for describing nonlinear binary protein adsorption equilibria.

[Spectral analysis and study of the microsome cytochrome P450 aromatase of Thais clavigera].

The microsomes were prepared from the viscera masses of Thais clavigeras. It is well known that there are some main components in microsome cytochrome P450 aroamtase, including cytochrome P450, cytochrome b5 and NADPH-cytochrome P450 reductase. So the contents of cytochrome P450 and cytochrome b5, and the activity of NADPH-cytochrome P450 reductase were determined by Shimadzu UV Visible spectrophotometer. And the microsomal proteins were analysed by SDS-PAGE. All the results indicated that there exists P450 arom in the T. clavigeras.

Analysis of mass transport models for protein adsorption to cation exchanger by visualization with confocal laser scanning microscopy.

The mass transfer of bovine serum albumin (BSA) to a cation exchanger, SP Sepharose FF, has been studied by finite batch adsorption experiments. The uptake curve was simulated with three mass transport models (i.e., effective pore diffusion model, surface diffusion model and Maxwell-Stefan model) incorporating the particle size distribution of the adsorbent particles. All the three models can simulate the uptake curves reasonably well. However, how well these models could simulate the real concentration profile within the adsorbent particle cannot be verified by the fitness of the models to the uptake curve. Thus, confocal laser scanning microscopy (CLSM) was used to visualize protein uptake to the porous adsorbent particles during the batch experiments. Using a fluorescent dye-labeled bovine serum albumin (BSA) for the dynamic adsorption experiments, the radial concentration profiles of the labeled BSA molecules into individual adsorbent particles at different times were obtained from the CLSM images. The protein distribution profiles within various particle diameters at different time were compared with the radial protein distributions predicted from the models. It reveals that surface diffusion model describes the intraparticle protein concentration profiles better than the other two models.