Effect of Phytochemical Compounds on Trichomonas tenax, an Oral Protozoan.

Trichomonas tenax is an oral protozoan with an estimated global pooled prevalence of 17% in the human population.1 Observational studies have demonstrated a significant statistical correlation between oral colonization by T. tenax and the progression of periodontal disease.2 Proposed pathogenic mechanisms for this protozoan include the production of tissue-damaging enzymes, induction of apoptosis in human cells, and dysbiosis of the oral microbiome.3 In patients for whom metronidazole (MTZ) is contraindicated, phytochemicals may offer a viable alternative for controlling T. tenax. Various plant extracts have shown promising in vitro activity against other trichomonads, such as T. vaginalis and Tritrichomonas foetus, as reviewed by Friedman et al.4.

Cytokine array analysis of mediators produced by human macrophages stimulated with Trichomonastenax.

The incidence of oral colonization by the protozoan Trichomonas tenax correlates with gingival inflammation and periodontitis in humans. To determine whether T. tenax might contribute to inflammation by eliciting cytokines from human cells, differentiated THP-1 (dTHP-1) macrophages were cultured with live or sonicated T. tenax trophozoites, and the conditioned media were assayed for 36 different mediators by a membrane-based cytokine array. Scanning densitometry of the membranes revealed that live T. tenax trophozoites stimulated secretion of interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF), IL-1ß, intercellular adhesion molecule-1 (ICAM-1), and IL-1 receptor antagonist (IL-1ra) from dTHP-1 macrophages. T. tenax lysates stimulated release of IL-8, MIF, and IL-1ra. Despite often being classified as a commensal organism, T. tenax elicited a wider variety of cytokines than the human urogenital pathogen, T. vaginalis, which elicited only IL-8 and MIF production from dTHP-1 cells.

Downregulation of miR-506-3p Facilitates EGFR-TKI Resistance through Induction of Sonic Hedgehog Signaling in Non-Small-Cell Lung Cancer Cell Lines.

Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment resistance remains the primary obstacle to the successful treatment of NSCLC. Although drug resistance mechanisms have been studied extensively in NSCLC, the regulation of these mechanisms has not been completely understood. Recently, increasing numbers of microRNAs (miRNAs) are implicated in EGFR-TKI resistance, indicating that miRNAs may serve as novel targets and may hold promise as predictive biomarkers for anti-EGFR therapy. MicroRNA-506 (miR-506) has been identified as a tumor suppressor in many cancers, including lung cancer; however, the role of miR-506 in lung cancer chemoresistance has not yet been addressed. Here we report that miR-506-3p expression was markedly reduced in erlotinib-resistant (ER) cells. We identified Sonic Hedgehog (SHH) as a novel target of miR-506-3p, aberrantly activated in ER cells. The ectopic overexpression of miR-506-3p in ER cells downregulates SHH signaling, increases E-cadherin expression, and inhibits the expression of vimentin, thus counteracting the epithelial-mesenchymal transition (EMT)-mediated chemoresistance. Our results advanced our understanding of the molecular mechanisms underlying EGFR-TKI resistance and indicated that the miR-506/SHH axis might represent a novel therapeutic target for future EGFR mutated lung cancer treatment.