Sinomenine regulates circTRPM7-related pathway to inhibit gastric cancer cell growth and metastasis.

Sinomenine has been found to have antitumor effects in a variety of cancers, including gastric cancer. Circular RNA (circRNA) is an important regulator of gastric cancer progression. However, it is not known whether Sinomenine mediates gastric cancer processes by regulating circRNA-related pathways. Quantitative real-time PCR was used to measure the expression of circTRPM7, microRNA-145-5p (miR-145-5p), and pre-B-cell leukemia homeobox 3 (PBX3). MTT assay, colony formation assay, EdU assay, transwell assay, wound-healing assay, and flow cytometry were used to detect cell proliferation, migration, invasion, and apoptosis. The expression of related proteins was detected by Western blot. Mechanically, the interaction of miR-145-5p with circTRPM7/PBX3 was validated by dual-luciferase reporter assay and RIP assay. Our study showed that circTRPM7 expression was reduced in Sinomenine-treated gastric cancer cells. Moreover, overexpression of circTRPM7 upregulated the growth and metastasis of Sinomenine-treated gastric cancer cells. CircTRPM7 could sponge miR-145-5p, and miR-145-5p reversed the effect of circTRPM7 on the growth and metastasis of Sinomenine-treated gastric cancer cells. PBX3 was the target of miR-145-5p, and knockdown of PBX3 could restore the in-miR-145-5p promotion effect on the malignant behavior of Sinomenine-treated gastric cancer cells. To sum up, our data indicated that Sinomenine played an antitumor role in gastric cancer cells via circTRPM7/miR-145-5p/PBX3 axis.

MiR-361-5p/abca1 and MiR-196-5p/arhgef12 Axis Involved in γ-Sitosterol Inducing Dual Anti-Proliferative Effects on Bronchial Epithelial Cells of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD), a progressive and irreversible respiratory disease, becomes the third leading cause of death and results in enormous economic burden on healthcare costs and productivity loss worldwide by 2020. Thus, it is urgent to develop effective anti-COPD drugs. MATERIALS AND METHODS: In the present study, two published GEO profiles were used to re-analyze and ascertain the relationships between circulating miRNAs and bronchial epithelial cells (BECs) mRNAs in COPD. The microRNA levels of miR-361-5p and miR-196-5p in plasma of COPD patients and healthy volunteers were detected by qRT-PCR. Next, the effects of γ-sitosterol (GS) on the expression of miR-361-5p and miR-196-5p and cell proliferation were investigated in BEC and H292 cell lines. Finally, whether specific miRNA-mRNA pathways involved in the effect of GS on BECs was assayed using Western Blot, real-time PCR and immunofluorescence. RESULTS: miR-196-5p and miR-361-5p were, respectively, up- and down-regulated in COPD patients compared with healthy controls. Luciferase assays demonstrated that miR-361-5p and miR-196-5p were, respectively, targeting abca1 and arhgef12 3'UTR in BEAS-2B cells. GS significantly suppressed miR-196-5p and promoted miR-361-5p levels in BEAS-2B cells and inhibited BECs proliferation in vitro. GS promoted miR-361-5p expression, which inhibited BCAT1 mRNA and protein levels and weaken mTOR-pS6K pathway, resulted in anti-proliferation in BEAS-2B cells. In addition, RhoA was activated by ARHGEF12 due to the inhibitory effect of miR-196-5p on arhgef12-3'UTR which was partially abolished by GS suppressing miR-196-5p expression. Activated RhoA further activated ROCK1-PTEN pathway and finally inhibited mTOR pathway, resulting in induced BECs proliferation. The anti-proliferation effect of GS was not observed in H292 cells. CONCLUSION: These findings indicate that miR-361-5p/abca1 and miR-196-5p/arhgef12 axis mediated GS inducing dual anti-proliferation effects on BECs.

Controlled Release of the Nimodipine-Loaded Self-Microemulsion Osmotic Pump Capsules: Development and Characterization.

The present study was intended to develop a controlled released osmotic pump capsule based on Nimodipine (NM)-loaded self-microemulsifying drug delivery systems (SMEDDSs) in order to improve the low oral bioavailability of NM. To optimize the NM-loaded SMEDDS composition, the experiments of NM solubility in different oils, the pseudo-ternary phase diagram experiments and the different drug loading experiments were conducted in the preliminary screening studies. Controlled release of NM required an osmotic pump capsule comprising a coated semi-permeable capsule shell, plasticizer, and pore-forming agent. NM release follows zero-order kinetics after oral administration. Polyethylene glycol content, used as a pore-forming agent, coating mass, and drug release orifice size were key factors affecting drug release behavior according to the single methods and were optimized through response surface methodology. The NM-loaded SMEDDS droplet size and the 1H NMR mass spectrogram of the novel capsule were determined. The droplet size of the reconstituted microemulsion was 39.9 nm and 1H NMR analysis showed NM dissolution in the microemulsion. The dissolution test performed on three batches of NM-SMEDDS capsules-prepared using optimal preparation methods-indicated the capsule to deliver a qualified drug delivery with a zero-order release rate. The results demonstrated that NM-loaded SMEDDSs were successfully developed and displayed a qualified release rate in vitro.

Curcumin co-treatment ameliorates resistance to gefitinib in drug- resistant NCI-H1975 lung cancer cells.

OBJECTIVE: To examine whether a combinative treatment with curcumin enhances the effects of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib on cell proliferation, clonogenic capacity and apoptosis in the drug-resistant lung cancer cell line NCI-H1975, and further investigate the molecular mechanisms involved. METHODS: NCI-H1975 cells were treated with curcumin and gefitinib alone or in combination, and cell proliferation, clonogenic capacity and apoptosis were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clone forming experiments, and flow cytometry, respectively, while p38, extracellular regulated protein kinase (ERK)1/2, and protein kinase B (AKT) phosphorylation were examined using Western blotting. RESULTS: Compared with the effects of either agent alone, the combination of curcumin and gefitinib had a stronger suppressive effect on proliferation and the clonogenic capacity (P < 0.05), and showed an increased ability to promote apoptosis (P < 0.05) and reduce p38, ERK1/2, and AKT phosphorylation (P < 0.05). CONCLUSION: Co-treatment of curcumin and gefitinib significantly improves the ability of gefitinib to inhibit cell proliferation, suppress the clonogenic capacity and enhance apoptosis in NCI-H1975 cells, and these effects are possibly mediated via a decrease in phosphorylation of proteins in downstream pathways of the epidermal growth factor receptor.

Splenic cystic lymphangioma in a young woman: case report and literature review.

Splenic cystic lymphangioma is extremely rare, with very few cases reported until now. Here, we report a case of cystic lymphangioma of the spleen in a young woman who was admitted for evaluation of abdominal pain and a mass lasting for two years. We present this case with emphasis on the problem of differential diagnosis and the difficulties of diagnostic certainty in the absence of histologic features.