Prebiotics-Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer.

While microbial-based therapy has been considered as an effective strategy for treating diseases such as colon cancer, its safety remains the biggest challenge. Here, probiotics and prebiotics, which possess ideal biocompatibility and are extensively used as additives in food and pharmaceutical products, are combined to construct a safe microbiota-modulating material. Through the host-guest chemistry between commercial Clostridium butyricum and chemically modified prebiotic dextran, prebiotics-encapsulated probiotic spores (spores-dex) are prepared. It is found that spores-dex can specifically enrich in colon cancers after oral administration. In the lesion, dextran is fermented by C. butyricum, and thereby produces anti-cancer short-chain fatty acids (SCFAs). Additionally, spores-dex regulate the gut microbiota, augment the abundance of SCFA-producing bacteria (e.g., Eubacterium and Roseburia), and markedly increase the overall richness of microbiota. In subcutaneous and orthotopic tumor models, drug-loaded spores-dex inhibit tumor growth up to 89% and 65%, respectively. Importantly, no obvious adverse effect is found. The work sheds light on the possibility of using a highly safe strategy to regulate gut microbiota, and provides a promising avenue for treating various gastrointestinal diseases.

Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/beta-catenin signaling pathway.

AIM: The Wnt signaling pathway plays a pivotal role in cellular developmental processes and human carcinogenesis. The aim of this study was to investigate the effects of quercetin on the growth of the colon carcinoma cell line and the regulation effect of quercetin on the Wnt/beta-catenin signaling pathway. METHODS: MTT assay was used to determine the reduction of cell viability of quercetin on SW480 cells and clone 26 cells. The apoptotic rate and cell-cycle analysis after treatment with quercetin was determined by flow cytometry. Effects of quercetin on mRNA expression of cyclin D(1) and survivin were detected by semiquantitative RT-PCR. After treatment with quercetin, the protein expression of cyclin D(1) and survivin in SW480 cells was analyzed by Western blot analysis. We built a Wnt/beta-catenin signaling pathway reporter gene model. The regulation effect of quercetin on the Wnt/beta-catenin signaling transcription was investigated by using this reporter gene model. RESULTS: Quercetin reduced cell viability in a dose- and time-dependent manner in SW480 and clone 26 cells. The percentages of SW480 cells and clone 26 cells at G(2)/M phase were increased significantly after treatment with 40 approximately 80 micromol/L quercetin for 48 hours. Quercetin induced the apoptosis of SW480 cells in a dose-dependent manner at the concentration of 20, 40, 60, anf 80 micromol/L. However, quercetin only induced the apoptosis of clone 26 cells at the concentration of 80 micromol/L. Quercetin downregulated transcriptional activity of beta-catenin/Tcf in SW480 cells transiently transfected with the TCF-4 reporter gene. Within 24 hours of treatment, a 160-mumol/L concentration of quercetin reduced beta-catenin/Tcf transcriptional activity by about 18-fold. Cyclin D(1) and the survivin gene were downregulated markedly by quercetin in a dose-dependent manner at both the transcription and protein expression levels. CONCLUSION: The results indicate that the molecular mechanism underlying the antitumor effect of quercetin in SW480 colon cancer cells is related to the inhibition of expression of cyclin D(1) and survivin as well as the Wnt/beta-catenin signaling pathway. Therefore, the Wnt/beta-catenin signaling pathway could be qualified as one of the promising targets for innovative treatment strategies of colorectal cancer.

A two-photon excited O2-evolving nanocomposite for efficient photodynamic therapy against hypoxic tumor.

This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (Ⅱ) complex (Ru(bpy)32+) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O2 generation can be triggered via two-photon irradiation from iron-doped carbon nitride (Fe-C3N4) for the first time. While exposured to two-photon laser, Ru(bpy)32+ was activated to generate singlet oxygen (1O2) and Fe-C3N4 was triggered to split water for oxygen supply in the mean time. Owing to the injection of photoinduced electrons from excited Ru(bpy)32+ to Fe-C3N4, O2 generation by Fe-C3N4 was significantly accelerated. After accumulation of the nanocomposite by enhanced permeability and retention (EPR) effect, FCRH was demonstrated to alleviate the tumorous hypoxia and consequently enhance the antitumor efficacy of PDT. Furthermore, tumor metabolism evaluations explained the capability of the nanocomposite in reducing intratumoral hypoxia. Our results provide a new diagram for ameliorating the hypoxic tumor microenvironment and accelerating 1O2 generation under two-photon excitation, which will find great potential for spatiotemporally controlled tumor treatment in vivo.

Artificial Super Neutrophils for Inflammation Targeting and HClO Generation against Tumors and Infections.

Neutrophils are powerful effector leukocytes that play an important role in innate immune systems for opposing tumor progression and ameliorating pathogen infections. Inspired by their distinct functions against tumors and infections, the artificial "super neutrophils" are proposed with excellent inflammation targeting and hypochlorous acid (HClO) generation characteristics for targeting and eliminating malignant tumor cells and pathogens. The "super neutrophils" are fabricated by embedding glucose oxidase (GOx) and chloroperoxidase (CPO) into zeolitic imidazolate framework-8 (ZIF-8) for HClO generation via enzymatic cascades, and then encapsulating them with the neutrophil membrane (NM) for inflammation targeting. In vitro and in vivo results indicate that these artificial "super neutrophils" can generate seven times higher reactive HClO than the natural neutrophils for eradicating tumors and infections. The "super neutrophils" demonstrated here with easy fabrication and good neutrophil-mimicking property exhibit great potential for biomedical applications.

A two-photon fluorescent probe for exogenous and endogenous superoxide anion imaging in vitro and in vivo.

Herein, we report a novel quinoline derivative-based two-photon fluorescent probe 6-(dimethylamino)quinoline-2-benzothiazoline (HQ), which is capable of tracking superoxide anion in organisms with specific "turn-on" fluorescence response based on extension of π-conjugations and moderate ICT process. The probe exhibited favorable photophysical properties, a broad linear range and high photostability. It can specifically detect superoxide anion with a significant fluorescence enhancement and great linearity from 0 to 500µM in PBS buffer. Furthermore, HQ shows low cytotoxicity and excellent photostability toward living cells and organisms, which was able to monitor endogenous superoxide anion fluxes in living cells and in vivo. For the first time, endogenous superoxide anion in lung inflammation was visualized successfully by using HQ through two-photon microscopy, and the probe HQ shows great potential for fast in-situ detecting of inflammatory response in live organisms.

[Study on the auxochrome of the electronic spectrum of organic compounds and its effect mechanism (I)].

This paper discusses the effect mechanism of auxochrome of electronic spectrum. The study proves that the auxochrome does not invariably make the maximum absorption wavelength of chromophore shift towards lower photon energy. For the transition of n-->pi*, the p orbit of the auxochrome interacts with the minimum antibonding empty orbit(pi*), which will make the energy of pi* increase, while the p orbit of the auxochrome is perpendicular to the n orbit of chromophore, and the energy of the n orbit will remain steady ultimately, so the transition energy of n-->pi* will increase. For the transition of pi-->pi*, the interaction of p orbit of the auxochrome and maximum bonding orbit (pi) of the chromophore forms new orbits, so the energy of the maximum bonding orbit in new orbits will increase. In some compounds, the increase is higher than those of pi*, so the transition energy of pi-->pi* will decrease and absorption wavelength will shift towards lower photon energy, which, however, is reverse in other compounds.

[Study on the auxochrome of the electronic spectrum of organic compounds and its effect mechanism (II)].

The interaction between the p orbit of the auxochrome, the maximum bonding orbit (pi) and the minimum antibonding orbit (pi*) of the chromophore forms three new molecular orbit, among which the antibonding orbit (pi*') has the highest energy that is higher than those of the original pi*. The maximum occupied orbit (pi') will have energy lower or higher than those of pi according to different auxochrome and chromophore, and the energy of n orbit will remain steady, because the n orbit of the original chromophore is perpendicular to the p orbit of the auxochrome and the interaction is negligeable. As a result, the absorption wavelength of transition n-->pi* will shift towards higher photon energy, but for transition pi-->pi*, the absorption wavelength will shift towards either lower or higher photon energy, depending on the species of auxochrome and chromophore.

A new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease.

This study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (HFMD). In this study, 1104 clinically diagnosed HFMD patients were included. Enterovirus 71 (EV71), coxsackievirus A16 (CA16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (PCR) or reverse transcriptase PCR (RT-PCR). To evaluate the immune activation in HFMD patients, 8 cytokines and IgM antibodies to EV71 and CA16 from mild and severe patients were detected. Our results indicated that the severity of HFMD may affect the pathogen detection. The lower positive rates of enterovirus and respiratory viruses in severe HFMD cases by RT-PCR were probably related to stronger immune response. Therefore, immunological tests such as ELISA are essential supplements to PCR or RT-PCR in order to increase pathogen diagnosis in HFMD, especially in severe cases.

[The effect on the differentiation and maturation of dendritic cells by lupane acetate of cortex periplocae].

AIM: To investigate the effect of lupane acetate of cortex periplocae (CPLA) on the differentiation, maturation and immune activity of human peripheral blood mononuclear cell (PBMC)-derived dendritic cells (DCs) in vitro. METHODS: PBMC isolated from human peripheral blood was cultured with GM-CSF, IL-4 for 5 d and stimulated with TNF-alpha (as positive control) or CPLA to induce DCs. The morphological characteristics of DC were observed under inverted microscope and transmisson electron microscope. The expressions of CD1a, CD83, CD80 and CD86 were analyzed by flow cytometry. IL-12, IFN-gamma production in the culture supernatant of DCs was detected by ELISA. MTT method was used to determine the proliferation of T cells stimulated by DCs. RESULTS: After 10-days culture with cytokines and CPLA, PBMC developed into mature DCs with typical morphological characteristics and high expressions of CD1a, CD83, CD80 and CD86 on the cellular surface (P<0.05). CPLA enhanced IL-12 and IFN-gamma production by DCs (P<0.05). CPLA-treated DCs markedly stimulated proliferation of T cells (P<0.05). CONCLUSION: CPLA may induce the differentiation and maturation of DC, up-regulate cytokines production and increase the immune activity of DC.