Combination of Talazoparib and Calcitriol Enhanced Anticancer Effect in Triple-Negative Breast Cancer Cell Lines.

Monotherapy for triple-negative breast cancer (TNBC) is often ineffective. This study aimed to investigate the effect of calcitriol and talazoparib combination on cell proliferation, migration, apoptosis and cell cycle in TNBC cell lines. Monotherapies and their combination were studied for (i.) antiproliferative effect (using real-time cell analyzer assay), (ii.) cell migration (CIM-Plate assay), and (iii.) apoptosis and cell cycle analysis (flow cytometry) in MDA-MB-468 and BT-20 cell lines. The optimal antiproliferative concentration of talazoparib and calcitriol in BT-20 was 91.6 and 10 µM, respectively, and in MDA-MB-468, it was 1 mM and 10 µM. Combined treatment significantly increased inhibition of cell migration in both cell lines. The combined treatment in BT-20 significantly increased late apoptosis (89.05 vs. control 0.63%) and S and G2/M populations (31.95 and 24.29% vs. control (18.62 and 12.09%)). Combined treatment in MDA-MB-468 significantly increased the S population (45.72%) and decreased G0/G1 (45.86%) vs. the control (26.79 and 59.78%, respectively). In MDA-MB-468, combined treatment significantly increased necrosis, early and late apoptosis (7.13, 33.53 and 47.1% vs. control (1.5, 3.1 and 2.83%, respectively)). Talazoparib and calcitriol combination significantly affected cell proliferation and migration, induction of apoptosis and necrosis in TNBC cell lines. This combination could be useful as a formulation to treat TNBC.

Effect of Rice (Oryza sativa L.) Ceramides Supplementation on Improving Skin Barrier Functions and Depigmentation: An Open-Label Prospective Study.

Ceramides plays a crucial role in maintaining skin barrier function. Although foregoing evidence supported beneficial effects of topical ceramides for restoration of the skin barrier, studies on oral ceramides are extremely scarce, with most published data collected from in vivo and in vitro models. Thus, this study aimed to evaluate the efficacy of rice ceramides (RC) supplementation to improve skin barrier function and as a depigmenting agent through comprehensive clinical assessments. This study investigated the beneficial effects of orally administered RC supplementation in 50 voluntary participants. Skin hydration, firmness and elasticity, transepidermal water loss (TEWL), melanin index (MI), erythema index (EI), sebum production, pH, and wrinkle severity were assessed at baseline and during monthly follow-up visits. RC supplementation was found to significantly (p < 0.01) improve skin hydration, sebum production, firmness and elasticity, and wrinkle severity for three assessed areas, namely the left cheek, dorsal neck, and right inner forearm. Additionally, RC significantly (p < 0.01) reduced the rates of TEWL, levels of MI and EI. Analyses of data indicated that participants at older age were more responsive towards the effect of RC supplementation. Our findings suggest that RC supplementation can effectively improve skin barrier function, reduce wrinkle severity, and reduce pigmentation.

Polymorphisms in P53 and VEGFA genes in different subtypes of periorbital hyperpigmentation in a Malaysian Chinese population.

BACKGROUND/OBJECTIVES: The unknown pathogenesis of periorbital hyperpigmentation makes its treatment difficult. Existing evidence links p53 and VEGFA genes with skin hyperpigmentation. This study was aimed at (i) identifying the clinical pattern of periorbital hyperpigmentation; and (ii) detecting the presence of VEGFA and P53 single nucleotide polymorphism (SNPs) in different subtypes of periorbital hyperpigmentation in Malaysian Chinese. METHODS: A cross-sectional study was conducted among Malaysian Chinese. Clinical assessments were performed, and medical history was collected. Three regions of p53 and two of VEGFA were amplified by PCR followed by direct sequencing using saliva-extracted DNA. RESULTS: Eighty-four participants were recruited (average age 22.2 years). In the majority (n = 62), both eyelids were affected. Facial pigmentary, demarcation lines, tear trough and eye bags were not observed. Mixed (pigmented-vascular) was the most common subtype. Thirteen SNPs were found, nine of which are new. Only three out of 13 SNPs showed significant association with periorbital hyperpigmentation presentation. TA genotype in rs1437756379 (p53) was significantly more prevalent among participants with mixed subtype (P = 0.011) while AC genotype in rs1377053612 (VEGFA) was significantly more prevalent among pigmented subtype (P = 0.028). AA genotype in rs1479430148 (VEGFA) was significantly associated with allergic rhinitis in mixed subtype (P = 0.012). CONCLUSION: Mixed subtype was the most prevalent type of periorbital hyperpigmentation in the study population. Three polymorphisms in p53 and VEGFA genes were statistically linked with different clinical presentations of periorbital hyperpigmentation.