Changes in the composition of the fecal metabolome and gut microbiota contribute to intervertebral disk degeneration in a rabbit model.

PURPOSE: Lower back pain (LBP), mainly caused by intervertebral disk (IVD) degeneration (IDD), is widely prevalent worldwide and is a serious socioeconomic burden. Numerous factors may trigger this degenerative process, and microbial dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between IDD and the microbiome remains obscure. In this study, we investigated the gut microbiota composition and fecal metabolic phenotype and discussed the possible influences of microbiome dysbiosis on IDD. METHODS: Fecal DNA was extracted from 16 fecal samples (eight rabbit models with IDD and eight sex- and age-matched healthy controls) and analyzed by high-throughput 16S rDNA sequencing. The fecal samples were also analyzed by liquid chromatography-mass spectrometry-based metabolomics. Multivariate analyses were conducted for the relationship between the omics data and IDD, linear discriminant analysis effect size was employed for biomarker discovery. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the differential metabolites. The potential correlation between differential gut microbiota and metabolites was then assessed. RESULTS: The 16S rDNA sequencing results showed that the ß-diversity of the gut microbiota was significantly different between the IDD and control groups, with distinct abundance levels of dominant genera. Moreover, 59 metabolites were significantly upregulated and 91 were downregulated in IDD rabbits versus the controls. The KEGG enrichment analysis revealed that the top pathways remarkably impacted by IDD were tyrosine metabolism, amino sugar and nucleotide sugar metabolism, benzoate degradation, ABC transporters, ascorbate and aldarate metabolism, pantothenate and CoA biosynthesis, and pyrimidine metabolism. The correlation analysis revealed that DL-tyrosine and N-acetylmuramic acid were associated with multiple differential bacterial genera, including Helicobacter and Vibrio, which may play important roles in the process of IVD degeneration. CONCLUSION: Our findings revealed that IDD altered gut microbiota and fecal metabolites in a rabbit model. The correlation analysis of microbiota and metabolome provides a deeper understanding of IDD and its possible etiopathogenesis. These results also provide a direction and theoretical basis for the clinical application of fecal transplantation, probiotics, and other methods to regulate gut microbiota in the treatment of LBP caused by IDD.

Study on Gas Sorption and Iodine Uptake of a Metal-Organic Framework Based on Curcumin.

Medi-MOF-1 is a highly porous Metal-Organic framework (MOF) constructed from Zn(II) and curcumin. The obtained crystal was characterized using powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). A micrometer-sized crystal with similar morphology was successfully obtained using the solvothermal method. Thanks to its high surface area, good stability, and abound pores, the as-synthesized medi-MOF-1 could be used as a functional porous material to adsorb different gases (H2, CO2, CH4, and N2) and iodine (I2). The activated sample exhibited a high I2 adsorption ability of 1.936 g g-1 at room temperature via vapor diffusion. Meanwhile, the adsorbed I2 could be released slowly in ethanol, confirming the potential application for I2 adsorption.

A surgical decompression procedure for effective treatment of calcified lumbar disc herniation.

OBJECTIVE: To present our experience in managing calcified lumbar disc herniation (cLDH) using a surgical decompression procedure. METHODS: Patients who had low back pain radiating to the leg, were preoperatively diagnosed with cLDH by computed tomography and/or magnetic resonance imaging, and were treated with a surgical decompression procedure were studied. Those without cLDH or who were treated with a method other than decompression were excluded. The treatment outcome was analyzed using the visual analog scale (VAS) score, Oswestry Disability Index, and modified Macnab criteria. RESULTS: Thirty-seven patients aged 60.5 ± 9.6 years were evaluated. The VAS scores were significantly decreased 1 day after surgery and remained low at the 3-month and 1-year follow-ups. The Oswestry Disability Index was also significantly lower at the 3-month and 1-year follow-ups. Ninety-four percent of patients rated the results as "excellent" or "good" according to the modified Macnab criteria at the 3-month follow-up. The patients developed few postoperative complications and no recurrence during 1 year of follow-up. CONCLUSION: Our data suggest that the decompression approach is effective for management of cLDH at least in the short term (1 year) with respect to reducing pain and improving patient satisfaction with few complications.

The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma.

BACKGROUND: To date, the impact and potential molecular mechanisms of CLDN12 and its association with malignancy in osteosarcoma have not been determined. MATERIALS AND METHODS: In the present study, the expression profiles of CLDN12 in osteosarcoma cell lines and tissues were explored by immunohistochemistry. A fetal osteoblast cell line was transfected with a eukaryotic expression plasmid, and endogenous CLDN12 in osteosarcoma cells were silenced through an RNA interference (RNAi) method. These transfections were verified, and the activation state of Thr308 site in protein kinase B (Akt) was explored by Western blotting. Moreover, the malignant phenotype of osteosarcoma cells was evaluated by cell counting kit-8 (CCK-8), colony formation, Transwell, and wound-healing assays. Furthermore, osteoblast cells were treated with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 to determine the impact of the PI3K/Akt signaling pathway on cell migration ability. RESULTS: The results revealed that CLDN12 was overexpressed and localized in the cytoplasm of osteosarcoma cells, and its overexpression was associated with an unfavorable prognosis, irrespective of tumor node metastasis stage. In addition, the knockdown of CLDN12 in cultured osteosarcoma cells markedly attenuated cell proliferation and migration, as indicated by the Cell Counting Kit-8 assay, colony formation assay, scratch wound healing assay and Transwell migration assay. The results also demonstrated that the overexpression of CLDN12 increased the activation of Thr308 site in Akt in fetal osteoblast cells, and the PI3K inhibitor LY294002 partially decreased CLDN12-promoted proliferation and metastasis. CONCLUSION: In conclusion, the results of the present study indicated that CLDN12 promoted cell proliferation and migration through the PI3K/Akt signaling pathway in osteosarcoma cells, suggesting that CLDN12 may be a potential agent in the treatment of patients with osteosarcoma.

MicroRNA-155 inhibition up-regulates LEPR to inhibit osteoclast activation and bone resorption via activation of AMPK in alendronate-treated osteoporotic mice.

Osteoporosis is characterized by a progressive increase in bone fragility, leading to low bone mass and structural deterioration of bone tissue. MicroRNA-155 (miR-155) is highly expressed in osteoporosis. Thus, the current study aimed to investigate the effect of miR-155 on the inhibition of osteoclast activation and bone resorption by targeting leptin receptor (LEPR) through the adenosine monophosphate activated protein kinase (AMPK) pathway in alendronate-treated osteoporotic mice. An osteoporosis mouse model was established to examine the bone tension and bone density and the expression of miR-155 in osteoclasts. Binding sites between miR-155 and LEPR were verified. Osteoclasts in the treatment group were transfected with different mimic, inhibitor, vector, or siRNA for subsequent experiments. The expression of miR-155, LEPR, AMPK, p-AMPK, RANKL, OPG, M-CSF, RANK, TRAP, Bax, Bcl-2, and the contents of TNF-α and IL-1ß were all examined. The proliferation and bone resorption of osteoclasts were also detected. Mice with osteoporosis exhibited decreased bone density and bone tension, along with elevated expression of miR-155. LEPR was verified as a target gene of miR-155. Down-regulated miR-155 was found to increase the expression of LEPR, AMPK, p-AMPK, OPG, Bax, decrease expression of TNF-α, IL-1ß, RANKL, M-CSF, RANK, TRAP, Bcl-2, inhibit the cell proliferation and bone resorption of osteoclasts. Taken together, decreased miR-155 up-regulated LEPR via activation of AMPK, which ultimately repressed osteoclast activation and bone resorption of osteoclasts in alendronate-treated osteoporotic mice.

A highly porous medical metal-organic framework constructed from bioactive curcumin.

A highly porous bio-MOF, medi-MOF-1, constructed from Zn and the pharmaceutical ingredient curcumin has been successfully synthesized. It can display permanent porosity with a surface area as high as ca. 3002 m(2) g(-1), which exhibits great potential in bioapplications. Its ibuprofen delivery ability, biodegradation and cytotoxicity were also studied.

Target synthesis of a novel porous aromatic framework and its highly selective separation of CO(2)/CH(4).

A novel porous aromatic framework based on tetra-(4-anilyl)-methane and cyanuric chloride has been designed and synthesized successfully, which possesses permanent porosity and high selectivity of CO2 towards CH4.

Targeted synthesis of a 2D ordered porous organic framework for drug release.

A novel 2D porous organic framework based on the nucleophilic substitution of cyanuric chloride has been designed and synthesized successfully, which possesses an ordered structure, permanent porosity and drug release ability towards ibuprofen.