Vitamin D and Immunoglobulin E Status in Allergic Rhinitis Patients Compared to Healthy People.

Allergic rhinitis (AR) is a type of inflammatory condition that includes a group of symptoms, mainly affecting the nasal mucosa. Nasal obstruction, sneezing, stuffy or runny nose, in addition to swollen, itchy, red and watery eyes are the most common symptoms of the disease. These symptoms are triggered as a result of increased inflammatory mediators such as histamine and leukotrienes. Studies have recently shown the role of vitamin D (vit.D) in many allergic and immune conditions, where receptors for the active form of vit.D (1,25-dihydroxyvitamin D3) have been discovered on the surface of almost all types of inflammatory cells. Therefore, the present study was conducted to explore the level of vit. D in AR patients and its correlation with the severity of the disease. Two groups participated in the study; the first group included 49 patients who were diagnosed in a private otolaryngology clinic by the first author as having allergic rhinitis (AR group). The second one served as a control group and included 50 apparently healthy volunteers with no history of AR. The mean level of IgE and vit. D was found to be 326.3 and 10.2 ng/ml in the AR group, respectively, and 30.8 and 23.3 ng/ml in the control group, respectively. Ninety-three percent of AR patients have shown a deficiency in vit. D level, where 56% of this group showed severe deficiency. On the other hand, 34% of the control group has shown an insufficient level of vit. D. Additionally, 64% of AR patients have shown serum levels of IgE at values ranging between 100-299 ng/ml. Higher serum levels of IgE at values ranging between 300-599 ng/ml and 600-1000 ng/ml were observed in 25% and 11% of AR patients, respectively. The prevalence of low levels of vit. D in the AR group was significantly higher than that in the control group (P < 0.001). Vit. D deficiency is significantly related to severe AR symptoms and measuring serum vit. D level is recommended in the management plan of this group of patients.

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway.

Cardamonin is a natural chalcone that has been shown to exhibit high anticancer activity. In an attempt to discover analogues of cardamonin with enhanced anticancer activity, 19 analogues were synthesized and tested against A549 and HK1 cell lines. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin's phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19). Compound 19 was the most active analogue possessing IC50 values of 13.2µM and 0.7µM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. It was also able to significantly inhibit the migration of A549 and HK1 cells. Further mode of action studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell- cycle arrest in both cell lines. These events further led to the induction of apoptosis by the compound via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Moreover, 19 inhibited the expression levels of p-mTOR and p-4EBP1, which indicated that it exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway.