Oleuropin controls miR-194/XIST/PD-L1 loop in triple negative breast cancer: New role of nutri-epigenetics in immune-oncology.

Oleuropein, the main secoiridoid glucoside found in Olea europaea L., has attracted scientific community as a potential anticancer agent. Immunotherapy and RNA interference revolutionized cancer treatment. Success of PD-L1/PD-1 antibodies encouraged the investigation of PD-1/PD-L1 regulation by non-coding RNAs. This study aimed to verify the cytotoxic effect of oleuropein on MDA-MB-231 cell line and to unravel novel ceRNA interaction between miR-194-5p and XIST in breast cancer and their immunomodulatory effect on PD-L1 expression to propose a promising prophylactic and preventive role of Oleuropin in diet. For the first time, miR-194/Lnc-RNA XIST/PD-L1 triad was investigated in breast cancer, where miR-194 and PD-L1 levels were significantly upregulated in 21 BC-biopsies, yet XIST was downregulated. Ectopic expression of miR-194 enhanced cell function and viability with concomitant increase in PD-L1 expression yet XIST expression decreased, in contrast to miR-194 antagomirs that yielded opposite results. XIST knock-out elevated miR194-5p and PD-L1 levels. miR-194-5p mimics and XIST siRNAs co-transfection induced PD-L1 expression, while miR-194-5p mimics and TSIX siRNAs co-transfection showed opposite effect. Oleuropein showed anti-carcinogenic impact by decreasing miR-194 and PD-L1 levels while increasing XIST level. In conclusion, our study highlighted novel ceRNA interaction controlling PD-L1 expression in BC. Oleuropein is a promising nutraceutical for cancer therapy. Therefore, oleuropin represents a new nutri-epigenetic in immune-oncology that controls miR-194/XIST/PD-L1 loop in triple negative breast cancer.

Comparing the Efficacy of Mesotherapy to Topical Minoxidil in the Treatment of Female Pattern Hair Loss Using Ultrasound Biomicroscopy: A Randomized Controlled Trial.

The efficacy of mesotherapy in the treatment of female pattern hair loss (FPHL) has not yet been evaluated. Aim of the study was to compare the initial efficacy and safety of mesotherapy containing nutritional supplements to topical minoxidil 5% solution in FPHL. 30 patients with FPHL were randomly classified into two equal groups: Group A applied minoxidil 5% lotion twice daily; Group B was injected with mesotherapy once weekly. For both groups ultrasound biomicroscopy (UBM) was performed before and at the end of the 12th week of treatment. After treatment, no significant difference was found between both groups with regard to either improvement of hair density and hair loss (P=0.27 and 0.056, respectively), nor the degree of improvement of Ludwig's classification as assessed by the investigator (P=0.210). A significant difference was observed between both groups (P=0.001) with the highest degree of satisfaction in the mesotherapy group. In group A, no significant difference was found in the number of hair follicles or the diameter of the largest hair follicle (P=0.244 and 0.925, respectively). In group B, a significant difference was found in the number of hair follicles (P=0.001), with no significant difference in the diameter of the largest hair follicle (P=0.105). The mesotherapy group showed more improvement with regard to the increase in the number of the hair follicles after treatment (P=0.007). Limitation of the study is small sample size, and relatively short duration of treatment. Mesotherapy, containing nutritional supplements only, is an effective, more acceptable to patients, and more tolerable modality compared with topical minoxidil in the treatment of FPHL.