Urban particulate matter (UPM) exerts negative effects on various human organs. Transient receptor potential vanilloid 1 (TRPV1) is a polymodal sensory transducer that can be activated by multiple noxious stimuli. This study aimed to explore the effects of the UPM 1648a on the expression of TRPV1, and its regulatory mechanisms in HaCaT cells. UPM enhanced TRPV 1 promoter-luciferase reporter activity. UPM also increased expression of the TRPV 1 gene as evidenced by increased mRNA and protein levels of TRPV 1. In addition, elucidation of the underlying mechanism behind the UPM-mediated effects on TRPV 1 expression revealed that UPM can upregulate expression of the TRPV1 gene by activating activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). The UPM treatment also altered Ca2+ influx and cell proliferation, as well as production of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). In addition, these UPM-induced effects were attenuated by SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC). However, SP600125 and PD98059 did not alter the UPM-induced effects. Taken together, these findings indicate that UPM upregulates expression of the TRPV 1 gene, which is mediated by the p38 mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways and suggest that UPM is a potential irritant that can induce skin processes such as aging and inflammatory responses.

Epithelial-mesenchymal transition (EMT) features are associated with pathological severity in the progression and metastasis of various cancer types, including bile duct cancer (BDC). Our previous study demonstrated that ursodeoxycholic acid (UDCA) blocked the EGFR-MAPK signaling pathway and inhibited the invasion of BDC cells. The present study was performed to determine whether UDCA inhibits EMT and promotes the expression of E-cadherin to inhibit the invasion and aggressiveness of BDC. In addition, the present study aimed to confirm that the primary mechanism of inhibition of EMT by UDCA is related to the EGFR axis. Human extrahepatic BDC cells were cultured. The effect of UDCA on cell proliferation was evaluated using MTT assays. A cell death ELISA kit was used to measure apoptosis, and western blot assays or immunofluorescence staining assays measured the expression levels of various target proteins. The mRNA expression of Slug and ZEB1 was evaluated via reverse transcription-quantitative PCR. The invasiveness of BDC cells was estimated by invasion assays and western blot assays for focal adhesion kinase (FAK). UDCA inhibited the proliferation of BDC cells as effectively as gefitinib (an EGFR inhibitor), and the combination of UDCA and gefitinib revealed an additive effect on the proliferation of cells. UDCA and gefitinib induced apoptosis, and the combination of UDCA and gefitinib demonstrated an additive effect on apoptosis in BDC cells. UDCA restored the E-cadherin expression inhibited by EGF and suppressed N-cadherin expression increased by EGF as effectively as gefitinib. UDCA suppressed the Slug and ZEB1 mRNA expression induced by EGF in BDC cells. UDCA suppressed the invasiveness of BDC cells and FAK expression linked to the invasiveness of BDC. In conclusion, UDCA enhanced E-cadherin expression and suppressed N-cadherin expression through inhibition of the EGF-EGFR axis, contributing to the inhibition of EMT and invasiveness in BDC cells. Therefore, UDCA may be applied as an adjuvant or palliative antineoplastic agent and as a therapeutic option to enhance the effect of other chemotherapeutics.

The LTBI rate in the present study was much higher than that estimated from other contact investigations. To minimise the risk of nosocomial TB transmission to neonates, screening and management of TB in health care workers should be strengthened.

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