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Achieving selective release of chemical anticancer agents and improving therapeutic efficacy has always been a hot spot in the field of cancer research, yet how to achieve this remains a great challenge. In this work, we constructed a novel chemical anticancer agent (named MCLOP) by introducing naphthalimide into the skeleton of methylene blue (MB). Under the stimulation by cellular hypochlorous acid (HClO) and visible light, selective release of active naphthalimide can be achieved within breast cancer cell lines, the release process of which can be tracked visually using near-infrared fluorescence of MB (685 nm). More importantly, we developed biotinylated curcumin (Cur-Bio) as a new chemosensitizer, which significantly enhanced the ability of MCLOP to induce autophagic cell death of breast cancer cells. This synergistic treatment strategy exhibited an excellent anti-proliferation effect on breast cancer cells in vitro, three-dimensional (3D) cell sphere model, and mouse tumor model in vivo. This work provides a new strategy for the treatment of breast cancer and also opens new opportunities for the efficient treatment of cancer with curcumin-based chemosensitizer.

Hydrogen polysulfide (H2Sn, n > 1), a member of reactive sulfur species (RSS), is primarily generated during the crosstalk between H2S and reactive oxygen species (ROS), which plays important role in physiological and pathological processes. Ferroptosis is a new non-classical mode of cell death, in which ROS-associated lipid peroxidation and iron-dependent accumulation are the main features. However, the biological effects of H2Sn on ferroptosis and the detailed mechanisms of action remain poorly understood. Thus, there is an urgent need to develop highly selective and sensitive chemical tools for monitoring H2Sn in living cells. Herein, we develop a two-photon fluorescent probe (PSP) for specifically imaging H2Sn in live cells and tumor spheroids. This probe exhibited a sensitive and selective response to H2Sn, which had been used for imaging exogenous and endogenous H2Sn in living cells by confocal imaging and high content imaging. PSP exhibits excellent photo-stability and two-photon imaging performance when irradiating at 880 nm in 3D HeLa multicellular tumor spheroids. Importantly, our studies revealed that H2Sn levels were significantly up-regulated during ferroptosis. These excellent properties ensure that PSP is a promising two-photon probe for exploring the biological and pathological effects of H2Sn during ferroptosis.

Aim: The aim of this study was to evaluate tacrolimus population pharmacokinetics and investigate factors that explain tacrolimus variability in adult heart transplant patients. Methods: A total of 707 tacrolimus concentrations from 107 adult heart transplant patients were included in model development. The effects of demographic, clinical factors and CYP3A5 genotype on tacrolimus clearance were evaluated using a nonlinear mixed-effects modeling. 24 patients with 106 tacrolimus concentrations were used for external validation. Results: The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and elimination. The estimated apparent clearance and volume of distribution of tacrolimus were 13.7 l/h and 791 l, respectively. Tacrolimus apparent clearance was significantly reduced in CYP3A5 nonexpressers (CYP3A5*3/*3), concomitant with azole antifungal drugs and Wuzhi capsule (WZ). A predictive performance was further confirmed in an external validation by Bayesian estimation. Recommended dose regimens were obtained by simulations based on the established model. Conclusion: This is the first population pharmacokinetic study conducted in Chinese heart transplant recipients. These findings are of great importance with regards to tacrolimus dose optimization in heart transplantation patients.

Hypochlorite, as one of reactive oxygen species, has drawn much attention due to its essential roles in special biological events and disorders. The exogenous hypochlorite remains a risk for human, animals and plants. In this work, a novel water soluble quinolin-containing nitrone derivative T has been developed for fluorometric sensing hypochlorite. The response mechanism of T towards ClO− was reported for the first time. In comparison with the reported sensors for ClO−, the sensor T in this work exhibited advantages including high selectivity (80 fold over other analytes), rapid response (within 5 s) and lipid-water distribution transformation (LogP from 2.979 to 6.131). Further biological applications suggested that T was capable of monitoring both exogenous and endogenous ClO− in living cells. The imaging in Arabidopsis thaliana indicated that the absorption and transmission of ClO− in plant could be monitored by this sensor through the chlorine-related mechanism. This work might raise referable information for further investigations in the physiological and pathological events in both tumor and plants.

Received January 19, 2010, from the Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Revision requested January 26, 2010. Revised manuscript accepted for publication February 3, 2010. Address correspondence to You-Bin Deng, MD, PhD, Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Rd, 430030 Wuhan, China. E-mail: ybdeng2007@hotmail.com Case Report

The etiology of flank pain sometimes experienced during the administration of ultrasound contrast agents is unknown. The aim of this study was to investigate whether microbubble ultrasound contrast agents are retained within the renal microcirculation, which could lead to either flow disturbance or local release of vasoactive and pain mediators downstream from complement activation.Retention of lipid-shelled microbubbles in the renal microcirculation of mice was assessed by confocal fluorescent microscopy and contrast-enhanced ultrasound imaging with dose-escalating intravenous injection. Studies were performed with size-segregated microbubbles to investigate physical entrapment, after glycocalyx degradation and in wild-type and C3-deficient mice to investigate complement-mediated retention. Urinary bradykinin was measured before and after microbubble administrations. Renal contrast-enhanced ultrasound in human subjects (n = 13) was performed 7 to 10 min after the completion of lipid microbubble administration.In both mice and humans, microbubble retention was detected in the renal cortex by persistent contrast-enhanced ultrasound signal enhancement. Microbubble retention in mice was linearly related to dose and occurred almost exclusively in cortical glomerular microvessels. Microbubble retention did not affect microsphere-derived renal blood flow. Microbubble retention was not influenced by glycocalyx degradation or by microbubble size, thereby excluding lodging, but was reduced by 90% (P.01) in C3-deficient mice. Urinary bradykinin increased by 65% 5 min after microbubble injection.Lipid-shelled microbubbles are retained in the renal cortex because of complement-mediated interactions with glomerular microvascular endothelium. Microbubble retention does not adversely affect renal perfusion but does generate complement-related intermediates that are known to mediate nociception and could be responsible for flank pain.

To analyse the mode of inheritance and clinical characteristics of retinitis pigmentosa (RP) patients with consanguineous marriage.RP patients were recruited for this study in Ningxia Eye Hospital from September 2009 to July 2011. All patients received complete ophthalmic examination. The mode of inheritance were determined based on family history and marriage history. Clinical features were characterized by complete ophthalmic examinations including visual acuity, macular OCT, visual field and electroretinogram (ERG).A total of 143 individuals with RP (33 families) were recruited. Based on analysis of family history and marriage history, 20 RP families (23 patients) had consanguineous marriage history accounted for 60.6% RP families (16.1% RP patients). There were 4 patients (from 4 families) diagnosed as Usher syndrome. In 20 RP families with consanguineous marriage history, 7 families (35.0%) were Hui ethnicity and 13 families (65%) were Han ethnicity. The marriages of 15 families were between first cousins and 3 families were between second cousins, only 2 families were between half cousins matrimony. Of 23 RP patients, 12 were males and 11 were females. The average age of onset was 11.4 ± 6.8 years and the average age of recruitment was (32.0 ± 13.5) years. The best-corrected visual acuity was less than 0.6 in 78.2% patients. According to the features of the fundus, 13 patients were classical retinitis pigmentosa and 10 patients were retinitis pigmentosa sine pigmento. Visual field examination showed that all patients had varying degrees of peripheral visual field defect. Retinal neuroepithelial layer of macular and peripheral retina became thinner and retinal photoreceptors were disappeared. The average thickness of macular fovea was (186.1 ± 78.7) µm on right eyes and (187.4 ± 76.3) µm on left eyes.The incidence of RP with consanguineous marriages was high in Ningxia Region. The mode of inheritance of RP patients with consanguinity is autosomal recessive. The common marriage pattern of consanguinity is between first cousins. The age of onset is early and the ocular fundus changes of some patients are atypical, this should be paid attention clinically.