Inhibitory effects of catalpol on DNCB-induced atopic dermatitis and IgE-mediated mast cells reaction.

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation. Catalpol is an iridoids, possessing anti-inflammatory, antioxidant, and neuroprotective activities. It can be added to food as a dietary supplement. To evaluate the effects and mechanisms of catalpol on AD, both in vitro and in vivo studies were conducted. It was found that catalpol downregulated the phosphorylation of Lyn and Syk to inhibit various downstream pathways, including intracellular Ca2+ elevation, cytokines generation, and histamine release, which ultimately controlled mast cell (MCs) degranulation. The results showed that catalpol alleviated AD-like skin lesions and MC infiltration via regulation of pro-Th2 and Th2 cytokines in vivo. Furthermore, this compound reduced the levels of IgE in AD mice and improved allergic reactions in PCA mice. The results provided that catalpol was potentially developed as a dietary supplement to improve AD and other atopic diseases.

Measurement Properties of the Simplified Chinese Version of the Lumbar Spine Instability Questionnaire for Patients With Low Back Pain in Mainland China.

STUDY DESIGN: A prospective study. OBJECTIVE: To develop a simplified Chinese version of Lumbar Spine Instability Questionnaire (SC-LSIQ) and test its measurement properties. SUMMARY OF BACKGROUND DATA: The LSIQ has been translated into several languages. Different versions of LSIQ have proved good reliability and validity in evaluating patients with low back pain. However, there is no simplified Chinese version of LSIQ (SC-LSIQ). MATERIALS AND METHODS: The SC-LSIQ has been translated into a simplified Chinese version according to a standard procedure. A total of 155 patients with low back pain completed the SC-LSIQ along with Oswestry Disability Index, Roland-Morris disability questionnaire, Tampa Scale for Kinesiophobia, and visual analogue scale (VAS). The internal consistency, test-retest reliability, and validity of SC-LSIQ were then calculated to evaluate the measurement properties of SC-LSIQ. RESULTS: The results of SC-LSIQ demonstrated that there was no ceiling or floor effect detected. The Cronbach α coefficient of 0.911 determined a well internal consistency. The intraclass correlation coefficient (0.98) presented an excellent reliability of SC-LSIQ. The Pearson correlation coefficient (r) showed that the SC-LSIQ was excellent correlated to Oswestry Disability Index (r=0.809), Roland-Morris disability questionnaire (r=0.870), and Tampa Scale for Kinesiophobia (r=0.945,). Furthermore, it moderately correlated to visual analogue scale (r=0.586). CONCLUSION: The SC-LSIQ features good internal consistency, reliability, and validity for evaluating Chinese patients with LBP. Results suggest that the SC-LSIQ can be appropriately applied to patients with LBP in routine clinical practice.

Baicalin Mitigates the Neuroinflammation through the TLR4/MyD88/NF-κB and MAPK Pathways in LPS-Stimulated BV-2 Microglia.

Baicalin (BA) is a major flavone from Scutellaria baicalensis Georgi and has showed significant curative effects in Parkinson's and Alzheimer's diseases. In the present study, we investigated the effects of BA on antineuroinflammation and related signaling cascade in lipopolysaccharide- (LPS-) induced BV-2 microglial model. The results showed that BA significantly attenuated inflammatory mediators (NO, iNOS, IL-1ß, COX-2, and PGE2) and suppressed the expression of miR-155. More crucially, BA could regulate the expression of related proteins in Toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear factor κB (NF-κB) pathway and suppress the phosphorylation of mitogen-activated protein kinase (MAPK) family. In addition, molecular docking analysis indicated that BA binds to the amino acids Lie 63 and Tyr 65 of TLR4 by π-σ and π-π T-shaped interaction. Thus, BA suppressed the LPS-stimulated neuroinflammation in BV-2 microglia by blocking the TLR4-mediated signal transduction through TLR4/MyD88/NF-κB and MAPK pathways and inhibiting the miR-155 expression. Our findings demonstrated that BA could be a valuable therapeutic for the treatment of neuroinflammation and neurodegenerative diseases.

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host-guest interaction for drug delivery.

A new water-soluble hexacarboxylated tribenzotriquinacene derivative (TBTQ-CB6) was synthesized and used as a supramolecular drug carrier to load the model anticancer drugs dimethyl viologen (MV) and doxorubicin (DOX) via host-guest interactions. The drugs could be effectively released by spermine (SM), a molecule overexpressed in cancer cells, through host-guest competitive substitution since TBTQ-CB6 has a stronger binding affinity toward SM than MV and DOX. The host-guest interactions of the complexes of TBTQ-CB6 with MV, DOX and SM were investigated by NMR spectroscopy and fluorescence spectroscopy. The association stoichiometry of the complexes of TBTQ-CB6 with MV, DOX, and SM was found to be 1:1 with association constants of K a = (7.67 ± 0.34) × 104 M-1, K a = (6.81 ± 0.33) × 104 M-1, and K a = (5.09 ± 0.98) × 105 M-1, respectively. The competitive substitution process was visualized by NMR titration. This novel TBTQ-based host-guest drug delivery system may have potential use in supramolecular chemotherapy.

Water-soluble host-guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres.

A sugar-functionalized water-soluble tribenzotriquinacene derivative bearing six glucose residues, TBTQ-(OG) 6 , was synthesized and its interaction with C60 and C70-fullerene in co-organic solvents and aqueous solution was investigated by fluorescence spectroscopy and ultraviolet-visible spectroscopy. The association stoichiometry of the complexes TBTQ-(OG) 6 with C60 and TBTQ-(OG) 6 with C70 was found to be 1:1 with binding constants of K a = (1.50 ± 0.10) × 105 M-1 and K a = (2.20 ± 0.16) × 105 M-1, respectively. The binding affinity between TBTQ-(OG) 6 and C60 was further verified by Raman spectroscopy. The geometry of the complex of TBTQ-(OG) 6 with C60 deduced from DFT calculations indicates that the driving force of the complexation is mainly due to the hydrophobic effect and to host-guest π-π interactions. Hydrophobic surface simulations showed that TBTQ-(OG) 6 and C60 forms an amphiphilic supramolecular host-guest complex, which further assembles to microspheres with diameters of 0.3-3.5 µm, as determined by scanning electron microscopy.

NQO1-selective activated prodrugs of combretastatin A-4: Synthesis and biological evaluation.

Tumor-specific prodrug treatment renders the exclusive delivery of antitumor agents with the lowest untoward effects. In this work, we reported the synthesis and biological assessment of four NQO1-activatable combretastatin A-4 prodrugs constituted by active drug CA-4, different self-immolating linkers, and NQO1-responsive trigger groups. The in vitro antiproliferative activities showed that prodrug 4 displayed greater selective toxicity toward the tumor cells that overexpressed NQO1, taxol-resistant A549 cells, hypoxia-exposed A549 and HepG2 cells, and incurred lower damage to normal cells in comparison with combretastatin A-4, prodrugs 1, 2, and 3. Moreover, based on a mechanistic study, NQO1 triggered prodrug 4 to effectively liberate the parent drug combretastatin A-4 and kill tumor cells. Furthermore, we also demonstrated that prodrug 4 exerted a stronger anticancer effect and greater safety than combretastatin A-4 under in vivo conditions. Hence, from the above results, NQO1 can be used as a specific delivery system for releasing anticancer agents; besides, prodrug 4 can serve as a candidate lead for developing specific anticancer agents.

LncRNA SNHG3 promotes clear cell renal cell carcinoma proliferation and migration by upregulating TOP2A.

LncRNA plays a vital role in many diseases, and abnormal expression of LncRNA has been reported in many types of tumors. In this study, we analyzed the available public TCGA and GEO databases, and found that the expression of SNHG3 was increased in clear cell renal cell carcinoma (ccRCC), which was positively correlated with many clinicopathological parameters, and the higher expression of SNHG3 predicted worse clinical prognosis. Functional experiments indicated that knockdown of SNHG3 could significantly inhibit the proliferation and metastasis of ccRCC in vitro and in vivo. Subsequently, through luciferase reporter assays, qPCR and rescue experiments, it was found that SNHG3 could bind to miR-139-5p, thereby up-regulating the expression of its target gene TOP2A, and play a role in promoting tumor progression in ccRCC. The correlation analysis showed that there was a significant positive correlation between the expression of SNHG3 and TOP2A, and both of them were significantly negative correlated with the expression of miR-139-5p. Our work suggested that the SNHG3/miR-139-5p/TOP2A axis plays an important role in the proliferation and metastasis of ccRCC, and was expected to be a new biomarker for diagnosis, prognosis and a target for treatment of ccRCC.

Paeonol Suppresses Neuroinflammatory Responses in LPS-Activated Microglia Cells.

In this work, we assessed the anti-inflammatory effects of paeonol (PAE) in LPS-activated N9 microglia cells, as well as its underlying molecular mechanisms. PAE had no adverse effect on the viability of murine microglia N9 cell line within a broad range (0.12∼75 µM). When N9 cell line was activated by LPS, PAE (0.6, 3, 15 µM) significantly suppressed the release of proinflammatory products, such as nitric oxide (NO), interleukin-1ß (IL-1ß), and prostaglandin E2 (PGE2), demonstrated by the ELISA assay. Moreover, the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly reduced in PAE-treated N9 microglia cells. We also examined some proteins involved in immune signaling pathways and found that PAE treatment significantly decreased the expression of TLR4, MyD88, IRAK4, TNFR-associated factor 6 (TRAF6), p-IkB-α, and NF-kB p65, as well as the mitogen-activated protein kinase (MAPK) pathway molecules p-P38, p-JNK, and p-ERK, indicating that PAE might act on these signaling pathways to inhibit inflammatory responses. Overall, we found that PAE had anti-inflammatory effect on LPS-activated N9 microglia cells, possibly via inhibiting the TLR4 signaling pathway, and it could be a potential drug therapy for inflammation-associated neurodegenerative diseases.

New eudesmane sesquiterpenes from Alpinia oxyphylla and determination of their inhibitory effects on microglia.

The fruits of Alpinia oxyphylla are used as healthcare products for the protection on neurons and prevention of dementia. Two new noreudesmane sesquiterpenoids, (5R,7S,10S)-5-hydroxy-13-noreudesma-3-en-2,11-dione (1) and (10R)-13-noreudesma-4,6-dien-3,11-dione (2), and a new eudesmane sesquiterpenoid, (5S,8R,10R)-2-oxoeudesma-3,7(11)-dien-12,8-olide (3), as well as 12 known sesquiterpenoids, were isolated from the fruits of A. oxyphylla. The structures of the new compounds (1-3) were elucidated on the basis of spectroscopic data and circular dichroism experiments. All isolates were evaluated their neuroprotective potential by inhibitory assay on nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production in lipopolysaccharide (LPS)-induced mouse microglia BV-2 cells.