A countercurrent chromatography solvent system based on deep eutectic solvents for separation of cis- and trans-crocetin from Gardenia jasminoides Ellis.

Due to the structural similarity and large difference in concentration, the separation of trans- and cis-crocetin has been challenging, and the cis-crocetin is usually neglected. In this work, a countercurrent chromatography method was developed for the quick separation of trans-crocetin and cis-crocetin from the hydrolytic extract of Gardenia jasminoides Ellis. High purity of trans-crocetin (>95%) and cis-crocetin (>91%) were prepared simultaneously for the first time through a novel biphasic system based on deep eutectic solvents, n-heptane/n-butyl alcohol/13 mmol/L Na2 CO3 in water/acetamide-benzyltrimethylammonium chloride (4:1, mol/mol) (4:7:9:1, v/v). The addition of deep eutectic solvent significantly improved the separation efficiency. The two targets can be easily recovered from the separation system through simple acidification and precipitation. It has potential for preparative separations on a large scale.

Predictors for Poor Outcomes After Percutaneous Endoscopic Lumbar Discectomy: A Retrospective Study of 241 Patients.

OBJECTIVE: Percutaneous endoscopic lumbar discectomy (PELD) is a popular surgical procedure for the treatment of lumbar disc herniation (LDH). However, a small proportion of patients will have poor surgical outcomes. We sought to identify the predictors for poor outcomes after PELD. METHODS: A total of 241 patients who had undergone PELD were followed up. Their numerical rating scale (NRS) for pain and Oswestry Disability Index scores were analyzed. They were divided by outcome (excellent, good, fair, poor) using the MacNab criteria. Their clinical history, physical examination, imaging, and surgical findings were compared among the groups. Ordinal logistic regression analysis was used to identify independent predictors for poor outcomes. RESULTS: The preoperative mean total NRS for back pain, NRS for leg pain, and Oswestry Disability Index scores were 4.3 ± 2.6, 5.6 ± 2.5, and 52.1% ± 23.0%. At 2 years after PELD, the corresponding scores had decreased to 1.2 ± 1.7, 0.9 ± 1.5, and 8.4% ± 11.2% (P < 0.001). The excellent, good, fair, and poor outcome rates were 44.4%, 31.5%, 17.4%, and 6.6%, respectively. Ordinal logistic regression analysis revealed that 2-level PELD (P = 0.001), a history of lumbar fusion (P = 0.007), and Modic changes (P = 0.011) were independent predictors for poor outcomes. Numbness was an independent predictor for excellent outcomes (P = 0.014). CONCLUSIONS: PELD appears to be an effective surgery for LDH. Two-level PELD, a history of lumbar fusion, and Modic changes at the same level were independent predictors for poor outcomes after PELD. Patients with LDH with numbness were more likely to have excellent outcomes.

MicroRNA-105 is involved in TNF-α-related tumor microenvironment enhanced colorectal cancer progression.

TNF-α is a central proinflammatory cytokine contributing to malignant tumor progression in tumor microenvironment. In this study, we found the upregulation of miR-105 in colorectal cancer was associated with aggressive phenotype, and the enhanced expression of miR-105 was required for TNF-α-induced epithelial-mesenchymal transition (EMT). The expression of miR-105 was remarkably stimulated by TNF-α in a time-dependent manner using real-time qPCR analysis. Inhibition of miR-105 remarkably weakened the aggressive effects of TNF-α through preventing the activation of NF-κB signaling and the initiation of EMT. Furthermore, miR-105 was demonstrated directly targeted on the 3'-UTRs of RAP2C, a Rap2 subfamily of small GTP-binding protein. Consistently, suppression of RAP2C stimulated the role of miR-105, which dramatically promoted the invasion and metastasis of CRC cells. Thalidomide, a TNF-α and NF-κB inhibitor, significantly weakened the metastasis and homing capacity of miR-105-overexpressed CRC cells in nude mice. Our investigation initiatively illustrated the modulatory role of miR-105 in TNF-α-induced EMT and further CRC metastasis. We also offer a better understanding of TNFα-induced metastasis and suggest an effective therapeutic strategy against CRC metastasis.

Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/ß-catenin signaling pathway.

The Wnt/ß-catenin pathway is known to contribute to colorectal cancer (CRC) progression, although little is known about the contribution of ß-catenin on this process. We investigated the role of miR-490-3p, which was recently reported to suppress tumorigenesis through its effect on Wnt/ß-catenin signaling. We found that hypermethylation of the miR-490-3p promoter down-regulates miR-490-3p expression in CRC tissue. Gain- and loss-of-function assays in vitro and in vivo reveal that miR-490-3p suppresses cancer cell proliferation by inducing apoptosis and inhibits cell invasiveness by repressing the initiation of epithelial-to-mesenchymal transition (EMT), a key mechanism in cancer cell invasiveness and metastasis. The frequently rearranged in advanced T-cell lymphomas (FRAT1) protein was identified as a direct target of miR-490-3p and contributes to its tumor-suppressing effects. miR-490-3p appears to have an inhibitory effect on ß-catenin expression in nuclear fractions of CRC cells, whereas FRAT1 expression is associated with the accumulation of ß-catenin in the nucleus of cells, which could be weakened by transfection with miR-490-3p. Our findings suggest that the miR-490-3p/FRAT1/ß-catenin axis is important in CRC progression and provides new insight into the molecular mechanisms underlying CRC. They may help to confirm the pathway driving CRC aggressiveness and serve for the development of a novel miRNA-targeting anticancer therapy.