Role of IL-5 in asthma and airway remodelling.

Asthma is a common and burdensome chronic inflammatory airway disease that affects both children and adults. One of the main concerns with asthma is the manifestation of irreversible tissue remodelling of the airways due to the chronic inflammatory environment that eventually disrupts the whole structure of the airways. Most people with troublesome asthma are treated with inhaled corticosteroids. However, the development of steroid resistance is a commonly encountered issue, necessitating other treatment options for these patients. Biological therapies are a promising therapeutic approach for people with steroid-resistant asthma. Interleukin 5 is recently gaining a lot of attention as a biological target relevant to the tissue remodelling process. Since IL-5-neutralizing monoclonal antibodies (mepolizumab, reslizumab and benralizumab) are currently available for clinical use, this review aims to revisit the role of IL-5 in asthma pathogenesis at large and airway remodelling in particular, in addition to exploring its role as a target for biological treatments.

Dental Caries-A Hiding Niche for Helicobacter Pylori in Children.

Background: Helicobacter pylori (H. pylori) is one of the human pathogens proven to be present in the oral cavity due to microaerophilic nature of the dental biofilm. The present study aimed to investigate the presence of H. pylori in cavitated carious lesions of children by polymerase chain reaction (PCR). Study design: Forty-eight children aged between 4 to 7-years attending outpatient Pediatric clinic were enrolled in the study. Caries status and caries severity were assessed using the dmft and ICDAS caries index. Dentine samples were collected for DNA isolation for the detection of H. pylori by PCR. Results: H. pylori was detected among 30% of children with severe caries lesions detected by PCR. Overall, the mean ± SD of the dmft score for H. pylori positive children was higher compared to the negative control. Amongst the H. pylori-positive group, the decayed (mean-dt) number of teeth were significantly higher (p<0.05) than the other group. Moreover, association between severity of caries lesions (codes 5 and codes 6) and presence of H. pylori were significant (p<0.05) when compared negative group. Conclusion: The results demonstrate presence of H. pylori in the cavitated, non-gastric niche of children with severe caries, which possibly could serve as a reservoir for microbial dissemination to other sites of the body.

Estrogen-induced hypomethylation and overexpression of YAP1 facilitate breast cancer cell growth and survival.

Increased expression of Yes-associated protein-1 (YAP1) was shown to correlate with reduced survival in breast cancer (BC) patients. However, the exact mechanism of YAP1 regulation in BC cells remains ambiguous. Genomic sequence search showed that the promoter region of the YAP1 gene contains CpG Islands, hence the likelihood of epigenetic regulation by DNA methylation. To address this possibility, the effect of estrogen (17ß estradiol; E2) on YAP1 gene expression and YAP1 promoter methylation status was evaluated in BC cells. The functional consequences of E2 treatment in control and YAP1-silenced BC cells were also investigated. Our data showed that E2 modulates YAP1 expression by hypomethylation of its promoter region via downregulation of DNA methyltransferase 3B (DNMT3B); an effect that seems to facilitate tumor progression in BC cells. Although the effect of E2 on YAP1 expression was estrogen receptor (ER) dependent, E2 treatment also upregulated YAP1 expression in MDA-MB231 and SKBR3 cells, which are known ER-negative BC cell lines but expresses ERα. Functionally, E2 treatment resulted in increased cell proliferation, decreased apoptosis, cell cycle arrest, and autophagic flux in MCF7 cells. The knockdown of the YAP1 gene reversed these carcinogenic effects of E2 and inhibited E2-induced autophagy. Lastly, we showed that YAP1 is highly expressed and hypomethylated in human BC tissues and that increased YAP1 expression correlates negatively with DNMT3B expression but strongly associated with ER expression. Our data provide the basis for considering screening of YAP1 expression and its promoter methylation status in the diagnosis and prognosis of BC.