Smartphone-based photochemical sensor for multiplex determination of glucose, uric acid, and total cholesterol in fingertip blood.

A smartphone-based photochemical biosensor capable of realizing multiplex detection of glucose, uric acid (UA), and total cholesterol (TC) is reported here for the first time. The system was composed of a photochemical dongle, a cloud-enabled smartphone, and disposable test strips. The dongle was controlled using a microcontroller unit and was designed to convert the reflected light's intensities into optoelectronic signals for analytes quantification. Only 30 µL of the fingertip blood is needed to complete accurate and reliable measurements within 2 minutes. A cloud-enabled smartphone is connected to the dongle via Bluetooth to serve as a data receiver, and users can obtain the test results for proactive health management or remote diagnosis, while powering the dongle. We believe the proposed biosensor will contribute a lot to the point-of-care-testing and has promising prospects in contributing to the development of the Internet of Medical Things.

Synthesis and anti-tumor activity evaluation of salinomycin C20-O-alkyl/benzyl oxime derivatives.

Seventeen C20-O-alkyl/benzyl oxime derivatives were synthesized by a concise and effective method. Most of these derivatives showed tens to several hundred nanomolar IC50 values against HT-29 colorectal, HGC-27 gastric and MDA-MB-231 breast cancer cells, whose antiproliferative activity is 15-240 fold better than that of salinomycin. The C20-oxime etherified derivatives can coordinate potassium ions, and further adjust the cytosolic Ca2+ concentrations in HT-29 cells. The significant improvement of the potency should be attributed to the better ion binding and transport ability of the modified derivatives. In addition, the C20-O-alkyl/benzyl oxime derivatives showed much better selectivity indexes (SI) than salinomycin, indicating that they present lower neurotoxic risk.

Biological characteristics of Chinese precocious strain of eimeria acervulina and its immune efficacy against different field strains.

In this study, the biologic characteristics of one experimental precocious strain of Eimeria acervulina and seven field isolates from different geographic locations in China were compared, and the immune efficacy of two precocious strains against coccidiosis in chickens was assessed to explore their potential use as coccidiosis vaccines. All the different strains were purified by single oocyst separation and their monospecificity was confirmed using E acervulina-specific PCR assays. The average sizes of E. acervulina oocysts were 18.28-20.19 X 14.09-14.79 microm and the shape indexes were from 1.28 to 1.40. The prepatent periods ranged from 93 to 115 hr, except for the Heyuan precocious strain (HYP; 75 hr). Chickens infected with Huadu field strain (GHD) produced the highest oocyst output whereas HYP induced the lowest level. When inoculated with 50,000 sporulated oocysts or more, the average weight gains of infected chickens were reduced, with apparent clinical symptoms. To assess the immunogenicity of precocious strains HYP and Baoding (BDP), birds were orally immunized and challenged with seven different field strains of E. acervulina. Body weight gain, fecal oocyst output, and gut lesion scores were compared to evaluate their vaccine potential. The results showed that the average body weight gains of chickens in all the vaccinated and challenged groups were higher than those of nonvaccinated and challenged groups. In general, oocyst shedding was reduced 34.39%-95.31% and gut lesion scores decreased 31.03%-86.21% compared with unvaccinated and challenged control chickens. In summary, this study indicated that the precocious strains of E. acervulina could induce a protective immune effect with various responses against coccidiosis caused by different field strains.

Potent salinomycin C20-O-alkyl oxime derivative SAL-98 efficiently inhibits tumor growth and metastasis by affecting Wnt/ß-catenin signal pathway.

The dysregulation of Wnt/ß-catenin signaling pathway is closely related to tumorigenesis, metastasis and cancer stem cell maintenance. Salinomycin is a polyether ionophore antibiotic that selectively eliminates cancer stem cells by inhibiting the Wnt/ß-catenin signal pathway. Salinomycin selectively target cancer stem cells, but the toxicity limits its further use. In this study, we explore the anti-tumor mechanism of one most active salinomycin C20-O-alkyl oximederivative SAL-98 and found that SAL-98 exerts 10 times higher anti-tumor and anti-CSCs activities compared with salinomycin, which induces cell cycle arrest, ER stress and mitochondria dysfunction and inhibits Wnt/ß-catenin signal pathway in vitro with high efficacy. Moreover, SAL-98 shows good anti-metastasis effect in vivo. In addition, SAL-98 demonstrates same anti-tumor activities as salinomycin with less 5 times concentration in vivo, the ER stress, autophagy and anti-CSCs effects were also confirmed in vivo. Mechanistically, SAL-98 inhibits the Wnt/ß-catenin signaling pathway associated with CHOP expression induced by ER stress, the induced CHOP disrupts the ß-catenin/TCF4 complex and represses the Wnt targeted genes. This study provides an alternative strategy for rational drug development to target Wnt/ß-catenin signaling pathway.

Inflammatory level under different p53 mutation status and the regulation role of curcumin in tumor microenvironment.

The inflammation is tightly associated with tumor development, promoting or inhibiting tumorigenesis. And mutant p53 is speculated to promote inflammation and tumorigenesis. The tumor associated macrophages are usually educated to present the anti-inflammatory profile to tune down antitumor immunity. However, the impact of p53 mutants on macrophages is not clear. Here, we compared the basal inflammatory level and macrophage profiles in tumor cells and tumor samples with different p53 mutations. Data revealed that a lower inflammatory level was maintained in immune organs and tumor cells with p53 point mutations than those with p53 null mutation. Using the tumor cell-derived conditional media to culture macrophages, we found that the media from cells with p53 mutations, especially the point mutations, could decrease M1 markers and inhibit phagocytosis, suggesting the p53 mutation promoted M2 profile polarization. To target the p53 mutation induced M2 macrophage polarization, we applied low-concentration curcumin to the tumor cells with different p53 mutations. The data showed that curcumin could inhibit STAT3 signal and decrease PPARγ and CSF1 in tumor cells and tumor samples. In vitro, the co-culture assays showed that the curcumin treatment shifted p53 mutation educated macrophages back towards M1 profile. In vivo, the curcumin-treated MEFs showed obvious tumor inhibition, and the tumor samples displayed inhibited M2 markers. Results suggested that curcumin could inhibit p53 mutation educated macrophage induction and suppress M2-promoted tumorigenesis. Our study illustrated the inflammatory level under different p53 status and the inflammatory regulated role of curcumin in tumor environment. This study might provide a potential method in tumor personalized treatment aiming immune therapy in different p53 status.