Uptake and Removal of Uranium by and from Human Teeth.

Uranium-238 (238U), a long-lived radiometal, is widespread in the environment because of both naturally occurring processes and anthropogenic processes. The ingestion or inhalation of large amounts of U is a major threat to humans, and its toxicity is considered mostly chemical rather than radiological. Therefore, a way to remove uranium ingested by humans from uranium-contaminated water or from the air is critically needed. This study investigated the uranium uptake by hydroxyapatite (HAP), a compound found in human bone and teeth. The uptake of U by teeth is a result of U transport as dissolved uranyl (UO22+) in contaminated water, and U adsorption has been linked to delays in both tooth eruption and development. In this present work, the influence of pH, contact time, initial U concentration, and buffer solution on the uptake and removal of U in synthetic HAP was investigated and modeled. The influence of pH (pH of human saliva, 6.7-7.4) on the uptake of uranyl was negligible. Furthermore, the kinetics were extremely fast; in one second of exposure, 98% of uranyl was uptaken by HAP. The uptake followed pseudo-second-order kinetics and a Freundlich isotherm model. A 0.2 M sodium carbonate solution removed all the uranyl from HAP after 1 h. Another series of in vitro tests were performed with real teeth as targets. We found that, for a 50 mg/L U in PBS solution adjusted to physiological pH, ∼35% of the uranyl was uptaken by the tooth after 1 h, following pseudo-first-order kinetics. Among several washing solutions tested, a commercially available carbonate, as well as a commercially available fluoride solution, enabled removal of all the uranyl taken up by the teeth.

Antitumor effects of Xi Huang pills on MDA­MB­231 cells in vitro and in vivo.

The management of patients with triple­negative breast cancer is challenging due to the lack of effective therapeutic options, aggressive behavior and relatively poor prognosis. Xi Huang pills (XHP) are a well­known traditional Chinese medicine that demonstrate anticancer activities. The aim of the present study was to investigate the antitumor effects of XHP on MDA­MB­231 cells in vitro and in vivo, and its potential underlying molecular mechanisms. In the present study, an MTT assay was used to evaluate the antiproliferative activity of XHP on MDA­MB­231 cells. In order to investigate the effects further, cell cycle distribution, apoptosis and mitochondrial membrane potential assays were performed, as well as western blot analyses. In addition, a tumor xenograft model was employed to investigate the effects of XHP in vivo. The results of the MTT assay demonstrated that the viability of MDA­MB­231 cells was markedly inhibited by XHP in a dose­ and time­dependent manner. The inhibitory effect of XHP on the viability of MDA­MB­231 cells was greater when compared with MCF­10A cells. An increase in apoptosis and loss of mitochondrial membrane potential was observed following 4, 8 and 12 mg/ml XHP treatment of MDA­MB­231 cells. The protein expression levels of cleaved caspase­3 were increased by 1.62­, 2.13­ and 2.19­fold, respectively, when compared with the untreated controls, whereas no effects on the expression of B­cell lymphoma 2 (Bcl­2) or Bcl­2­associated X protein (Bax) were observed. The results of the cell cycle distribution assay analysis demonstrated that XHP treatment arrested cells at the G2/M phase. In addition, XHP treatment decreased the expression of cyclin A and increased the expression of p21Cip1. In vivo experiments revealed that XHP inhibited the growth of MDA­MB­231 xenograft tumors without body weight loss, and demonstrated similar effects on the protein expression levels of cleaved caspase 3, cyclin A and p21Cip1 as observed in vitro. In conclusion, the viability of MDA­MB­231 cells was inhibited by XHP in a dose­dependent, time­dependent and cell­selective manner in vitro, and the potential underlying mechanisms may involve apoptosis and cell cycle arrest at the G2/M phase. XHP may induce apoptosis in MDA­MB­231 cells via the intrinsic pathway, which does not involve the Bcl­2/Bax ratio. G2/M phase arrest may have been due to the integrated action of decreased cyclin A expression and increased p21Cip1 expression. In addition, XHP inhibited the growth of xenograft tumors in the absence of body weight loss in vivo.

Multiple effects of Xihuang pill aqueous extract on the Hs578T triple-negative breast cancer cell line.

The management of triple-negative breast cancer (TNBC) is challenging due to the aggressive behavior, lack of therapeutic options and relatively poor prognosis. Xihuang pill (XHP) is a well-known Traditional Chinese Medicine with anticancer activity. The aim of the present study was to investigate whether the aqueous extract of XHP (AEXHP) has anti-proliferative activity against the Hs578T TNBC cell line, and to elucidate its molecular mechanisms of action. First, an MTT assay was used to evaluate the anti-proliferative activity of AEXHP on the Hs578T cell line; furthermore, the cell cycle distribution, mitochondrial membrane potential and apoptotic rate were determined by flow cytometry, and western blot analysis was used to assess the expression of apoptosis and cell cycle regulatory proteins to investigate the mechanisms of action. The results revealed that the cell viability was significantly inhibited by AEXHP in a dose- and time-dependent manner. Apoptosis and mitochondrial membrane potential loss were detected, and after treatment with 4, 8 and 12 mg/ml AEXHP for 24 h, cleaved caspase-3 was 1.70-, 1.81- and 1.84-fold of that of the control, while procaspase-3, procaspase-8, cleaved caspase-8, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and the Bcl-2/Bax ratio were not significantly affected. Cell cycle analysis revealed that treatment with AEXHP led to S-phase arrest of Hs578T cells. Furthermore, AEXHP treatment resulted in decreased expression of cyclin A and cyclin dependent kinase 2 (CDK2), and increased expression of cyclin E and p21Cip1, as compared to the control group. In conclusion, the viability of Hs578T cells was significantly inhibited by AEXHP in a dose- and time-dependent manner, the likely mechanisms of which being induction of apoptosis, probably via the intrinsic, Bcl-2-independent pathway, and cell cycle arrest in S phase due to decreased expression of cyclin A and CDK2, and increased expression of cyclin E and p21Cip1.