Functional characterization of the extranasal OR2A4/7 expressed in human melanocytes.

Olfactory receptors (ORs) were first described as specialized chemoreceptors in the nasal epithelium. In the last two decades, ORs have also been detected to be functionally expressed and active in different nonolfactory tissues of the human body, because they used to react to specific odour stimuli. In this study, we conducted a characterization of the extranasal OR2A4/7 expressed in primary human melanocytes and sections of the human skin. OR2A4/7 expression could be demonstrated at the transcript and protein level. We uncovered elevated intracellular cAMP and Ca2+ levels accompanied by elevated p38 and reduced p42/44 MAPK phosphorylation following odourant (cyclohexyl salicylate; CHS) stimulation of melanocytes. These results were associated with enhanced melanin biosynthesis in conjunction with the growth inhibition and differentiation of melanocytes. Our findings highlight the participation of OR2A4/7 in human primary melanocyte physiology and suggest an alternate mechanism that regulates melanogenesis.

Survival rates among women with ovarian cancers diagnosed in the area of Podkarpacie province in the years 1990-2015.

AIM OF THE STUDY: The objective of the study was to analyse the survival rate of women with malignant ovarian tumours in the years 1990-2015 in the Podkarpacie province. MATERIAL AND METHODS: The database used for calculations covered 2399 cancer incidences verified at the end of 2014. The estimated relative survival rates were calculated by means of the Hakulinen method. RESULTS: The number of recorded cases amounted to 196 in 2015 and was higher by 86.7% than in 1990. The rates of one-year, three-year, and five-year survival was 72.5%, 51.2%, and 42.4%, respectively. CONCLUSIONS: Survival rates of women with ovarian cancer in the Podkarpacie province are comparable to survivals calculated for the entire Poland region. Despite the low risk factor, women suffering from ovarian adenocarcinoma have lower survival rates than others, and as many as 42.5% of patients with adenocarcinoma were diagnosed in stage IV. Steps aimed at improvement of detectability of ovarian cancers in the earliest possible stage should be taken. This should increase survival rates in each age group.

Two olfactory receptors-OR2A4/7 and OR51B5-differentially affect epidermal proliferation and differentiation.

Olfactory receptors (ORs), which belong to the G-protein coupled receptor family, are expressed in various human tissues, including skin. Cells in non-olfactory tissues tend to express more than one individual OR gene, but function and interaction of two or more ORs in the same cell type has only been marginally analysed. Here, we revealed OR2A4/7 and OR51B5 as two new ORs in human skin cells and identified cyclohexyl salicylate and isononyl alcohol as agonists of these receptors. In cultured human keratinocytes, both odorants induce strong Ca2+ signals that are mediated by OR2A4/7 and OR51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces a cAMP-dependent pathway. Localization studies and functional characterization of both receptors revealed several differences. OR2A4/7 is expressed in suprabasal keratinocytes and basal melanocytes of the epidermis and influences cytokinesis, cell proliferation, phosphorylation of AKT and Chk-2 and secretion of IL-1. In contrast, OR51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27, AMPK1 and p38MAPK phosphorylation and interestingly, IL-6 secretion. These findings underline that different ORs perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair.

Olfactory signaling components and olfactory receptors are expressed in tubule cells of the human kidney.

Cells of the renal tubule system are in direct contact with compounds dissolved in the urine, such as short chain fatty acids (SCFA). Murine OR78, a member of the olfactory receptor (OR) family, is involved in SCFA-related regulation of renal blood pressure in mice. It is still unclear whether OR signaling has an impact on human renal physiology. In our study, we showed that OR51E1 and OR11H7, both of which can be activated by the SCFA isovaleric acid, are expressed in the HK-2 human proximal tubule cell line. We observed a transient increase in intracellular Ca2+ when isovaleric acid and 4-methylvaleric acid were added to HK-2 cells. The isovaleric acid-induced response was dependent on extracellular Ca2+ and adenylyl cyclase (AC) activation. Furthermore, we demonstrated that the canonical olfactory signaling components Gαolf and ACIII are co-localized with OR51E1. The number of cells responding to isovaleric acid correlated with the presence of primary cilia on HK-2 cells. OR51E1 protein expression was confirmed in the tubule system of human kidney tissue. Our study is the first to show the expression of ORs and olfactory signaling components in human kidney cells. Additionally, we discuss ORs as potential modulators of the renal physiology.

Does the Level of Air Pollution Affect the Incidence of Lung Adenocarcinoma in South-Eastern Poland?

The aim of this study was to assess the association of long-term exposure to particulate matter with aerodynamic diameter, PM2.5, PM10, NO2 and SO2 as well as CO, with lung adenocarcinoma (AD) in south-east Poland for the years from 2004 to 2014. The study group consisted of 4296 patients with lung adenocarcinoma and the level of selected pollutants. To analyse the data, a standard statistics for cohort data, that is a risk ratio (RR), was used. The dependencies occurring in the distribution of pollutants and cancer incidence were examined using Moran's I correlation coefficient. The current study suggests that PM10, NO2 and SO2 exposure as an air pollutant may increase female lung adenocarcinoma incidence. In men, the increased risk of adenocarcinoma lung cancer is affected by SO2 and PM10. A high morbidity rate in urban areas and suburbs may be connected with commuting from moderately polluted living areas to highly polluted working areas.

Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18.

G protein-coupled receptors (GPCRs) transduce external chemical cues into intracellular signals and are involved in a plethora of physiological processes, but knowledge regarding the function of these receptors in spermatozoa is limited. In the present study, we performed RNA-Seq and analyzed the expression of the all GPCRs except olfactory receptors in human spermatozoa. We revealed the expression of up to 223 different GPCR transcripts in human spermatozoa (FPKM > 0.1) and identified GPR18, a newly described cannabinoid receptor, together with GPR137 and GPR135, as one of the three most highly expressed GPCRs. To date, the expression of GPR18 was completely unknown in human spermatozoa. We confirmed GPR18 expression using RT-PCR and immuncytochemistry experiments and localized the GPR18 protein in the midpiece of human spermatozoa. Stimulation of human spermatozoa with the GPR18 ligand N-arachidonoylglycine induced the phosphorylation of 12 protein kinases, some of them are for example known to be involved in the acrosome reaction. In line with this, N-arachidonoylglycine affected the cytoskeleton by changing levels of F-actin and inducing the acrosome reaction in human spermatozoa in a concentration-dependent manner. Our results indicate that GPR18 might be involved in physiological processes of human spermatozoa, suggesting GPR18 to be a potential player in sperm physiology.