Ultraviolet B (UVB) irradiation is one of the most dangerous insults for skin and causes sunburn, erythema, photoaging and photocarcinogenesis. Curcumin (diferuloylmethane), a yellow spice derived from dried rhizomes of Curcuma longa, has been shown to possess significant anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant and anti-infective effects. However, the protective effects of curcumin against acute photo-damage are poorly understood. In this study, we investigated the photoprotective effects of curcumin against UVB-induced acute photo-damage in hairless mice and immortalized human keratinocytes (HaCaT). Topical application of curcumin significantly inhibited acute UVB (540 mJ cm , for 3 successive days)-induced inflammatory cells, collagen accrementition derangement and lipid peroxidation, and effectively induced NF-E2-related factor 2 (Nrf2) nuclear accumulation in uncovered (Uncv) hairless mice skin. Treatment of HaCaT cells with curcumin significantly attenuated acute UVB (300 mJ cm )-induced lactate dehydrogenase release, intracellular reactive oxygen species production and DNA damage, activated the expression of the phase II detoxifying enzymes and promoted DNA repair activity. The photoprotective effect provided by curcumin was potential associated with modulation of Nrf2-dependent antioxidant response. Our study suggested that curcumin is a potential agent for preventing and/or treating UV radiation-induced acute inflammation and photoaging.

Glioma, the most predominant primary malignant brain tumor, remains uncured due to the absence of effective treatments. Hence, it is imperative to develop successful therapeutic agents. This study aimed to explore the antitumor effects and mechanisms of ivermectin (IVM) in glioma cells in vitro and in vivo. The effects of IVM on cell viability, cell cycle arrest, apoptosis rate, and morphological characteristics were determined respectively by MTT assay/colony formation assay, flow cytometry, and transmission electron microscope. In addition, the expression levels of cycle‐related and apoptosis‐associated proteins were individually examined by Western blot analysis. Moreover, cell proliferation and apoptosis analyses were carried out by TUNEL, Ki‐67, cleaved caspase‐3, and cleaved caspase‐9 immunostaining assay. Our results demonstrated that IVM has a potential dosage‐dependent inhibition effect on the apoptosis rate of glioma cells. Meanwhile, the results also revealed that IVM induced apoptosis by increasing caspase‐3 and caspase‐9 activity, upregulating the expressions of p53 and Bax, downregulating Bcl‐2, activating cleaved caspase‐3 and cleaved caspase‐9, and blocking cell cycle in G0/G1 phase by downregulating levels of CDK2, CDK4, CDK6, cyclin D1, and cyclin E. These findings suggest that IVM has an inhibition effect on the proliferation of glioma cells by triggering cell cycle arrest and inducing cell apoptosis in vitro and in vivo, and probably represents promising agent for treating glioma.

Synergistic eŠects have previously been observed for a natural compound, tetrandrine (TET), with ‰uconazole (FLC) in vitro and in the treatment of Candida albicans-infected mice. To investigate the mechanisms of these synergistic eŠects, 16 strains of C. albicans from the same parent but with diŠerent FLC sensitivities were examined using ‰ow cytometry and ‰uorescent spectrophotometry. Rhodamine 123 (Rh123)-positive cells and intracellular Rh123 ‰uores-cence intensity were determined in accumulation/eOEux experiments involving no or a noncytotoxic dose of TET. Total RNA extracted from each strain was used to compare the expressions of drug eOEux pump genes in FLC-susceptible, -susceptible dose-dependent, and -resistant strains before and 24 h after TET administration. Accumulation experiments determined that mean percentages of Rh123-positive cells were 26.65％ (TET-free) and 70.99％ (TET 30 mg/ml), and mean respective intracellular Rh123 ‰uorescence intensities were 11.34 and 18.00. EOEux experiments showed that percentages of Rh123-positive cells were 1.79％ (TET free) and 42.57％ (TET 30 mg/ml), respectively, and respective mean intracellular Rh123 ‰uorescence intensities were 0.74 and 2.19. DiŠerences in MDR1, FLU1, CDR1, and CDR2 expression levels in the absence of TET were statistically signiˆcant ( p＜0.05) between FLC-susceptible, -susceptible dosedependent, and -resistant strains. Compared with TET-free conditions, 24 h TET-treated strains showed statistically diŠerent ( p＜0.05) expression of MDR1 (FLC-resistant strain), FLU1 (FLC-susceptible dose-dependent and -resistant strains), and CDR1 and CDR2 (FLC-susceptible, -susceptible dose-dependent, and -resistant strains). Thus TET can inhibit the C. albicans drug eOEux system and reduce drug eOEux. Its mechanism of action is related to the inhibition of expression of the drug eOEux pump genes MDR1, FLU1, CDR1, and CDR2.

Glioma is one of the most common types of primary brain tumors. Ivermectin (IVM), a broad-spectrum antiparasitic drug, has been identified as a novel anticancer agent due to its inhibitory effects on the proliferation of glioma cells in vitro and in vivo. However, the ability of IVM to induce autophagy and its role in glioma cell death remains unclear. The main objective of the present study was to explore autophagy induced by IVM in glioma U251 and C6 cells, and the deep underlying molecular mechanisms. In addition, we examined the effects of autophagy on apoptosis in glioma cells. In the present study, transmission electron microscopy (TEM), immunofluorescence, Western blot and immunohistochemistry were used to evaluate autophagy activated by IVM. Cell viability was measured by 3-(4,5-dimethylthiazol2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and colony formation assay. The apoptosis rate was detected by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Meanwhile, autophagy inhibition was achieved by using chloroquine (CQ). U251-derived xenografts were established for examination of IVM-induced autophagy on glioma in vivo. Taken together, the results of the present study showed that autophagy induced by IVM has a protective effect on cell apoptosis in vitro and in vivo. Mechanistically, IVM induced autophagy through AKT/mTOR signaling and induced energy impairment. Our findings show that IVM is a promising anticancer agent and may be a potential effective treatment for glioma cancers.

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