Multistimuli-responsive multicolor solid-state luminescence tuned by NH-dependent switchable hydrogen bonds.

Revealing the stimuli-responsive mechanism is the key to the accurate design of stimuli-responsive luminescent materials. We report herein the multistimuli-responsive multicolor solid-state luminescence of a new dicopper(I) complex [{Cu(bpmtzH)}2(µ-dppa)2](ClO4)2 (1), and the multistimuli-responsive mechanism is clarified by investigating its four different solvated compounds 1·2CH3COCH3·2H2O, 1·2DMSO·2H2O, 1·4CH3OH, and 1·4CH2Cl2. It is shown that luminescence mechanochromism is associated with the breakage of the hydrogen bonds of bmptzH-NH with counter-ions such as ClO4- induced by grinding, while luminescence vapochromism is attributable to the breaking and forming of hydrogen bonds of dppa-NH with solvents, such as acetone, dimethylsulfoxide, and methanol, caused by heating and vapor fuming. In addition, those results might provide new insights into the design and synthesis of multistimuli-responsive multicolor luminescent materials by using various structure-sensitive functional groups, such as distinct N-H ones, to construct switchable hydrogen bonds.

Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans.

Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

Thermo-, Mechano-, and Vapochromic Dinuclear Cuprous-Emissive Complexes with a Switchable CH3CN-Cu Bond.

A thermo-, mechano-, and vapochromic bimetallic cuprous-emissive complex has been reported, and the origin and application of its tri-stimuli-responsive luminescence have been explored. As revealed by single-crystal structure analysis, thermo- and vapochromic luminescence adjusted by heating at 60 °C and CH3CN vapor fuming, accompanied by a crystalline-to-crystalline transition, is due to the breaking and rebuilding of the CH3CN-Cu bond, as supported by 1H nuclear magnetic resonance (NMR), Fourier-transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), thermogravimetry (TG), and time-dependent density functional theory (TD-DFT) analyses of the CH3CN-coordinated species [Cu2(µ-dppa)2(µ-η1(N)η2(N,N)-fptz)(CH3CN)](ClO4)·H2O (1) and its CH3CN-removed derivative [Cu2(µ-dppa)2(µ-η1(N)η2(N,N)-fptz)](ClO4)·H2O (2). Luminescence mechanochromism, mixed with a crystalline-to-amorphous transition where the initial crystalline is different for 1 and 2, is mainly assigned as the destruction of the CH3CN-Cu bonding and/or the O···HNdppa and OH···Ntriazolyl hydrogen bonds. It is also suggested that a rational use of switchable coordination such as weak metal-solvent bonding is a feasible approach to develop multi-stimuli-responsive luminescent materials and devices.

A Mechanochromic and Vapochromic Luminescent Cuprous Complex Based on a Switchable Intramolecular π···π Interaction.

An in-depth study on a stimuli-responsive tetranuclear cuprous luminescent complex is reported and gives new insights into the origin and possible use of the observed stimuli-responsive luminescence. Its crystalline polymorphs with two different shapes are obtained by using different crystallization solvents and show distinct emissions, with one being blue emissive and the other being yellow emissive. Upon grinding, only the blue-emitting polymorph has a marked change in the emission color from blue to yellow, and its ground sample exhibits a yellow emission similar to that of the yellow-emitting polymorph. Interestingly, the yellow-emitting polymorph after exposure to acetone vapor can emit a blue emission and display luminescence mechanochromism similar to that of the blue-emitting polymorph. Single-crystal structural analyses of the two different polymorphs reveal the relationship between the mechanochromic luminescence and the geometrical configuration of the {Cu(µ-dppm)2Cu} unit and intramolecular "pyridyl/phenyl" π···π interactions, supported as well by their PXRD, FT-IR, TGA, and PL studies in various states and by TD-DFT analyses. The results demonstrate the different roles of switchable intramolecular π···π interactions and the geometrical configuration of the {Cu(µ-dppm)2Cu} unit in this stimuli-responsive luminescence and potential applications of such stimuli-responsive luminescence in optical sensing and anticounterfeiting encryption technologies and deepen the understanding of such stimuli-responsive luminescence originating from switchable intramolecular π···π interactions. In addition, it is clearly suggested that the rational utilization of switchable intramolecular π···π interactions is a feasible route for developing stimuli-responsive intelligent luminescent materials and devices.

Current status of oxacillin-susceptible mecA-positive Staphylococcus aureus infection in Shanghai, China: A multicenter study.

BACKGROUND: Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) represents an important issue, as its oxacillin susceptibility has contributed to misidentification by conventional susceptibility tests and consequently potential therapeutic failure, but limited data on the current status of OS-MRSA infection in Chinese hospitals are available. METHODS: This multicenter study performed a battery of susceptibility tests and diagnostic tests for 956 S. aureus isolates from 10 hospitals, including automated susceptibility testing on VITEK 2, broth microdilution, disk diffusion, and detection of PBB2a, mecA gene and mecC gene. For all identified OS-MRSA, multi-locus sequence typing (MLST), together with spa typing, SCCmec typing and PVL detecting, was carried out. RESULTS: OS-MRSA, most of which were from pediatric inpatients, represented 1.8% (17/956) of total isolates. Of these 17 OS-MRSA, 10 were ST59, followed by ST965 (3/17), and 11 carried SCCmec type IV, while 5 carried SCCmec type V, but only one was Panton-Valentine leucocidin (PVL)-positive, also, 16 had one or two point mutations within mecA promoter. OS-MRSA had inducible oxacillin resistance and significantly lower MDR (Multi-Drug Resistant) rate. We observed that the VITEK 2 system exhibited some deficiency in OS-MRSA detection, whereas cefoxitin disk diffusion was shown to be a reliable and cost-saving alternative and should be supplemented in detecting S. aureus with borderline oxacillin susceptible MICs. CONCLUSION: This study has characterized phenotypically and molecularly OS-MRSA in China, and provided insights into more effective management of OS-MRSA.

Reversible Mechanochromic Luminescence of Tetranuclear Cuprous Complexes.

Mechanochromic luminescence materials have attracted rapidly growing interest. Nevertheless, the designed synthesis of such materials remains a challenge, and there have been few examples based on weak intramolecular interactions. Herein, we report a new approach for preparing mechanochromic luminescence materials of Cu(I) complexes, i.e., constructing a photoluminescence system that bears a large coplanar multinuclear Cu(I) unit showing weak intramolecular π···π interactions with the planar rings of the coordinated ligands in the molecule. Using it, a series of novel mechanochromic luminescent tetranuclear Cu(I) complexes have been successfully designed and synthesized. As revealed by single-crystal X-ray crystallography, these Cu(I) complexes share an identical {Cu4[µ3-η2(N,N),η1(N),η1(N)-pyridyltetrazole]2}2+ planar fragment whose coplanar pyridyl rings exhibit weak intramolecular π···π interactions with the phenyl rings of the coordinated phosphine ligands in the molecule. All of these Cu(I) complexes exhibit reversible mechanochromic luminescence, which can be attributed to the change in the rigidity of the molecular structure resulting from the disruption and restoration of intramolecular π···π interactions between the pyridyl and phenyl rings triggered by grinding and CH2Cl2 vapor, as supported by powder X-ray diffraction and Fourier transform infrared spectrometry. In addition, the results might provide a new route for developing mechanochromic luminescence materials of Cu(I) complexes for intelligent responsive luminescent devices.

A Sublimable Dinuclear Cuprous Complex Showing Selective Luminescence Vapochromism in the Crystalline State.

A new sublimable dicopper(I) complex bearing 1,2-bis(diphenylphosphino)ethane and 5-trifluoromethyl-3-(2'-pyridyl)pyrazolate ligands has been designed and synthesized, and its crystalline solvated and nonsolvated compounds have also been obtained and investigated. It is shown that only the crystalline solvated compound exhibits reversible and selective luminescence vapochromism, arising from its unique "pyridyl/CH2Cl2/pyridyl" organic sandwich-like stacking arrangement revealed by X-ray crystallography, as supported by time-dependent density functional theory calculations. Additionally, the neutral Cu(I) complex has excellent thermal stability and sublimability, good solid-state luminescence properties, and TADF character, and it is suggested to be a good emitter for vapor-deposited organic light-emitting diodes.

Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response.

Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans, and that EFG1-Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the fungal burden and the levels of pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae, while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1-Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans.

MiR-187 overexpression inhibits cervical cancer progression by targeting HPV16 E6.

Aberrantly expressed microRNAs contribute to the initiation and progression of human cancer. MiRNA-187 has been reported in nasopharyngeal, renal, pancreatic, prostate, and esophageal cancer, and acts as a tumor suppressor or oncogene. However, the underlying function of miRNA-187 in cervical cancer remains largely unexplored. In the present study, we demonstrated significantly miRNA-187 down-regulation in cervical cancer tissues and cell lines compared to their normal counterparts. Kaplan-Meier analysis revealed that decreased miRNA-187 was closely associated with shorter overall survival and relapse-free survival. Gain- and loss-of-function studies showed that miRNA-187 suppressed cervical cancer cell proliferation, migration, and invasion, and promoted cervical cancer cell apoptosis. Furthermore, luciferase reporter assay determined that human papillomavirus 16 E6 was a direct functional target of miRNA-187. Taken together, our findings indicate the essential role of miRNA-187 in suppressing cervical cancer progression and indicate a novel link between miRNA-187 and human papillomavirus 16 E6 in cervical cancer.

Synthesis, structure, and photophysics of copper(i) triphenylphosphine complexes with functionalized 3-(2'-pyrimidinyl)-1,2,4-triazole ligands.

A series of new mononuclear and dinuclear copper(i) triphenylphosphine complexes with functionalized 3-(2'-pyrimidinyl)-1,2,4-triazole ligands have been synthesized and characterized, in which functionalized 3-(2'-pyrimidinyl)-1,2,4-triazole adopts neutral mono- and bis-chelating coordination modes and a mono-anionic bis-chelating binding manner due to the 1,2,4-triazolyl-NH deprotonation. All these Cu(i) complexes display a relatively weak low-energy absorption in a CH2Cl2 solution, ascribed to the charge-transfer transitions with appreciable MLCT character, as suggested by TD-DFT analyses. These Cu(i) complexes are all emissive in solution and in the solid state at ambient temperature, and their luminescence properties can be well modulated via the addition of the second {Cu(PPh3)2} unit and modification of 3-(2'-pyrimidinyl)-1,2,4-triazole involving the N-H deprotonation and the substituent variation of the 1,2,4-triazolyl ring. It is also demonstrated that introducing the trifluoromethyl group into the 1,2,4-triazolyl ring is helpful for enhancing the solid-state luminescence properties of the 1,2,4-triazole-based Cu(i) complexes, whereas the introduction of the tert-butyl group into the 1,2,4-triazolyl ring, the 1,2,4-triazolyl-NH deprotonation, and the use of the pyrimidinyl ring instead of the pyridyl ring are all unfavorable.

Luminescent Three- and Four-Coordinate Dinuclear Copper(I) Complexes Triply Bridged by Bis(diphenylphosphino)methane and Functionalized 3-(2'-Pyridyl)-1,2,4-triazole Ligands.

A new series of bimetallic Cu(I) complexes 1-5 triply bridged by a monoanionic or charge-neutral functionalized 3-(2'-pyridyl)-1,2,4-triazole in a µ-η1(N),η2(N,N) tridentate binding mode and two bis(diphenylphosphino)methane (dppm) ligands have been synthesized. Complexes 1-5 are singly or doubly charged dinuclear Cu(I) species with an eight-membered Cu2C2P4 ring of {Cu(µ-dppm)2Cu} unit, in which 3 and 4 adopt the boat-boat conformation, while 1, 2, and 5 display the chair-boat form. In these dimeric copper(I) complex cations, one of the two Cu(I) ions is four-coordinated, in a highly distorted N2P2 tetrahedral environment and the other is three-coordinated, in a distorted NP2 trigonal planar arrangement. All these Cu(I) complexes exhibit a comparatively weak low-energy absorption in CH2Cl2 solution, ascribed to the charge-transfer transitions with appreciable 1MLCT contribution, as suggested by time-dependent density functional theory (TDDFT) analyses. Complexes 1-5 display good emission properties in both solution and solid states at ambient temperature, which are well-modulated via structural modification of 3-(2'-pyridyl)-1,2,4-triazole, including the alteration of the substituent type (-CF3, -H, -CH3, and -C(CH3)3) and position (ortho-, meta-, and para-position). Furthermore, the variation of the substituent (-CF3 and -C(CH3)3) on the 5-site of the 1,2,4-triazolyl ring markedly influences the proton activity of the 1,2,4-triazolyl-NH, thus leading to the formation of both singly and doubly charged bimetallic Cu(I) species regulated by the NH ↔ N- conversion, resulting from NH deprotonation of the 1,2,4-triazolyl ring.

The Effect of PCDH15 Gene Variations on the Risk of Noise-induced Hearing Loss in a Chinese Population.

Noise-induced hearing loss (NIHL) is a complex disease caused by interactions between environmental and genetic factors. This study investigated whether genetic variability in protocadherin related 15 (PCDH15) underlies an increased susceptibility to the development of NIHL in a Chinese population. The results showed that compared with the TT genotype of rs11004085, CT/CC genotypes were associated with an increased risk of NIHL [adjusted odds ratio (OR) = 2.64; 95% confidence interval (CI): 1.14-6.11, P = 0.024]. Additionally, significant interactions between the rs11004085 and rs978842 genetic variations and noise exposure were observed in the high-level exposure groups (P < 0.05). Furthermore, the risk haplotype TAGCC was observed when combined with higher levels of noise exposure (P < 0.05). Thus, our study confirms that genetic variations in PCDH15 modify the susceptibility to NIHL development in humans.

Comparative investigation on the pharmacokinetics of geniposide in type 2 diabetic and normal rats after oral administration of Fructus Gradeniae extract.

Fructus Gradeniae, the fruit of Gardenia jasminoides Ellis, was used alone or in combination with other herb medicines in the treatment of type 2 diabetes mellitus in China for a long time. In present investigation, the HPLC method for the determination of geniposide in rat plasma was developed and validated, and the pharmacokinetics of geniposide in type 2 diabetic rats after oral administration of Fructus Gradeniae extract or pure was studied. The results showed that the pharmacokinetic profile (especially the area under the plasma concentration-time curve, AUC) of geniposide in type 2 diabetic rats after orally administered with Fructus Gradeniae extract or pure geniposide was remarkably different from that in normal rats. The results indicated that the increased AUC of geniposide in type 2 diabetic rats did not result from the effects of other components contained in Fructus Gradeniae. It could be speculated that the increased AUC of geniposide might result from the pathological state of type 2 diabetes mellitus which resulted in the pharmacokinetic alterations of geniposide.

Luminescent dinuclear copper(I) complexes bearing 1,4-bis(diphenylphosphino)butane and functionalized 3-(2'-pyridyl)pyrazole mixed ligands.

A family of new dinuclear Cu(i) complexes with 1,4-bis(diphenylphosphino)butane (dppb) and functionalized 3-(2'-pyridyl)pyrazole mixed ligands has been synthesized and characterized. It is revealed that all these Cu(i) complexes include a [Cu2(dppb)2](2+) framework with the two Cu(i) atoms doubly bridged by a pair of dppb to generate a fourteen-membered Cu2P4C8 ring, and functionalized 3-(2'-pyridyl)pyrazole adopts a neutral chelating coordination mode without the N-H bond cleavage of the pyrazolyl ring. All these dinuclear Cu(i) complexes display a relatively weak low-energy absorption in CH2Cl2 solution, which is closely related to the variation of the Cu-N and Cu-P bonds caused by the substituent on the pyrazolyl ring. These dinuclear Cu(i) complexes are all emissive in solution and solid states at ambient temperature, which can be well modulated through structural modification of 3-(2'-pyridyl)pyrazole. It is shown that introduction of the trifluoromethyl group into the pyrazolyl ring is helpful for enhancing the luminescence properties of Cu(i) pyrazole phosphine complexes.

How Work Organization Affects the Prevalence of WMSDs: A Case-control Study.

OBJECTIVE: In this study, we aimed at exploring the association between work-related musculoskeletal disorders (WMSDs) and work organization based on a case-control study. METHODS: A total of 1938 workers who claimed to suffer from WMSDs were selected from Beijing, Henan, Hubei, and the Guangdong province. The control group consisted of 2009 workers employed in similar industries without severe disease or musculoskeletal discomforts. We used a modified version of the questionnaire developed by the NMQ and the DMQ to investigate individual and work-related factors. RESULTS: A total of 13 variables (P<0.1) were selected by the chi-square test and finally, 7 variables entered into the equation, with 6 variables reaching statistical significance (P<0.05). The odds ratios (OR) of 'work changing with season' and 'sufficient rest time' did not reach 1 (0.749 and 0.441, respectively). In addition, 'sufficient rest time' seemed to be the stronger protective factor according to its higher standardized coefficient. And 'repetitive work every minute', 'constantly repetitive work' (every day), 'shortage of site personnel', and 'often switching shifts with others' seemed to be the risk factors. CONCLUSION: Work organization may have comprehensive effects on the occurrence of WMSDs. This pattern of associations suggests that further investigation into the mechanism of how work organization affects the prevalence of WMSDs is required.

Primary antibiotic resistance of Helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: a prospective serial study.

AIM: To determine the resistance patterns of Helicobacter pylori (H. pylori) strains isolated from patients in Beijing and monitor the change of antibiotic resistance over time. METHODS: In this prospective, serial and cross-sectional study, H. pylori cultures were successfully obtained from 371 and 950 patients (never receiving eradication) during 2009-2010 and 2013-2014, respectively. Resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin was determined by Epsilometer test. RESULTS: The resistance rates of isolates obtained during 2009-2010 were 66.8%, 39.9%, 34.5%, 15.4%, 6.7%, and 4.9% to metronidazole, clarithromycin, levofloxacin, rifampicin, amoxicillin and tetracycline, respectively; and the corresponding rates for isolates during 2013-2014 were 63.4%, 52.6%, 54.8%, 18.2%, 4.4% and 7.3%, respectively. The resistance rates to clarithromycin and levofloxacin were significantly increased after four years. In 2009-2010, 14.6% of H. pylori isolates were susceptible to all tested antibiotics, with mono (33.7%), double (28.3%), triple (16.7%), quadruple (6.2%), quintuple (0.3%) and sextuple resistance (0.3%) also being detected. In 2013-2014, 9.4% were susceptible to all tested antibiotics, and mono (27.6%), double (28.4%), triple (24.9%), quadruple (7.3%), quintuple (2.3%) and sextuple resistance (0.1%) was also observed. More multiple resistant H. pylori isolates were found during 2013-2014. Gender (to levofloxacin and metronidazole), age (to levofloxacin) and endoscopic findings (to clarithromycin) were independent factors influencing antibiotic resistance. CONCLUSION: H. pylori resistance to commonly used antibiotics in Beijing is high with increased multiple antibiotic resistance.

Complete mitochondrial genome of the common cutworm Spodoptera litura (Lepidoptera: Noctuidae).

We determined the complete mitochondrial genome of the common cutworm Spodoptera litura (Lepidoptera: Noctuidae), which is one of the most destructive polyphagous insect pests worldwide. The genome is 15,383 bp in length (GenBank accession number: KF701043) with an A+T content of 81.08%, and contains 37 typical animal mitochondrial genes (13 protein-coding genes, 2 rRNA genes and 22 tRNA genes) with the typical arrangement found in Lepidoptera. All the protein-coding genes (PCGs) start with ATN start codon except for cox1, which begins with CGA. Eight PCGs stop with complete termination codons (TAA or TAG), whereas five PCGs use incomplete stop codon T. The A+T-rich region is located between rrnS and trnM with a length of 326 bp and an A+T content of 93.87%, and harbors three tandem repeat elements.

Identification of Variable-Number Tandem-Repeat (VNTR) Sequences in Acinetobacter pittii and Development of an Optimized Multiple-Locus VNTR Analysis Typing Scheme.

OBJECTIVE: To develop a multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) assay for Acinetobacter pittii typing. METHODS: Polymorphic VNTRs were searched by Tandem Repeats Finder. The distribution and polymorphism of each VNTR locus were analyzed in all the A. pittii genomes deposited in the NCBI genome database by BLAST and were evaluated with a collection of 20 well-characterized clinical A. pittii strains and one reference strain. The MLVA assay was compared with pulsed-field gel electrophoresis (PFGE) for discriminating A. pittii isolates. RESULTS: Ten VNTR loci were identified upon bioinformatic screening of A. pittii genomes, but only five of them showed full amplifiability and good polymorphism. Therefore, an MLVA assay composed of five VNTR loci was developed. The typeability, reproducibility, stability, discriminatory power, and epidemiological concordance were excellent. Compared with PFGE, the new optimized MLVA typing scheme provided the same and even greater discrimination. CONCLUSION: Compared with PFGE, MLVA typing is a faster and more standardized alternative for studying the genetic relatedness of A. pittii isolates in disease surveillance and outbreak investigation.

[Prevention against and treatment of doxorubicin-induced acute cardiotoxicity by dexrazoxane and schisandrin B].

In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.

Inhibition of cell growth by BrMC through inactivation of Akt in HER-2/neu-overexpressing breast cancer cells.

We previously reported that chrysin (ChR) and its analogs induced cell cycle arrest and apoptosis in human estrogen receptor-positive/-negative breast cancer cells. However, it was unknown whether 8-bromo-7-methoxychrysin (BrMC), a novel synthetic ChR analog, inhibited the cell growth of human epidermal growth factor receptor 2 (HER-2)/neu-overexpressing breast cancers. In the present study, it was demonstrated that BrMC preferentially inhibited the cell viability of HER-2/neu-overexpressing MDA-MB-453 and BT-474 cells. Western blot analysis revealed that HER-2/neu expression and tyrosine phosphorylation were inhibited by BrMC in a concentration-dependent manner; whereas the proteasome inhibitor, MG-132, significantly prevented BrMC-induced HER-2/neu depletion and cell death in MDA-MB-453 cells. This directly indicated that BrMC-induced HER-2/neu depletion and cell growth inhibition was mediated by a proteasomal pathway. BrMC significantly downregulated the expression of cyclin D1, cyclin E and CDK4, followed by the suppression of protein kinase B phosphorylation and downstream effectors, GSK-3ß and ß-catenin. A colony formation assay also confirmed the growth-inhibitory effects of BrMC. Thus, these findings clearly demonstrate the anticancer activity of BrMC against human HER-2/neu-overexpressing breast cancer cells. Thus, these findings clearly demonstrate the anticancer activity of BrMC against human HER 2/neu-overexpressing breast cancer cells, and highlight BrMC as a promising candidate for breast cancer therapy.