Enterococcus faecalis is increasingly becoming an important nosocomial infection opportunistic pathogen. E. faecalis can easily obtain drug resistance, making it difficult to be controlled in clinical settings. Using bacteriophage as an alternative treatment to drug-resistant bacteria has been revitalized recently, especially for fighting drug-resistant bacteria. In this research, an E. faecalis bacteriophage named IME-EF1 was isolated from hospital sewage. Whole genomic sequence analysis demonstrated that the isolated IME-EF1 belong to the Siphoviridae family, and has a linear double-stranded DNA genome consisting of 57,081 nucleotides. The IME-EF1 genome has a 40.04% G+C content and contains 98 putative coding sequences. In addition, IME-EF1 has an isometric head with a width of 35 nm to 60 nm and length of 75 nm to 90 nm, as well as morphology resembling a tadpole. IME-EF1 can adsorb to its host cells within 9 min, with an absorbance rate more than 99% and a latent period time of 25 min. The endolysin of IME-EF1 contains a CHAP domain in its N-terminal and has a wider bactericidal spectrum than its parental bacteriophage, including 2 strains of vancomycin-resistant E. faecalis. When administrated intraperitoneally, one dose of IME-EF1 or its endolysin can reduce bacterial count in the blood and protected the mice from a lethal challenge of E. faecalis, with a survival rate of 60% or 80%, respectively. Although bacteriophage could rescue mice from bacterial challenge, to the best of our knowledge, this study further supports the potential function of bacteriophage in dealing with E. faecalis infection in vivo. The results also indicated that the newly isolated bacteriophage IME-EF1 enriched the arsenal library of lytic E. faecalis bacteriophages and presented another choice for phage therapy in the future.
Abstract. Liver-specific microRNA-122 (miR-122) is involved in the replication of hepatitis C virus (HCV) and its potential as a target for antiviral intervention was recently assessed. However, the use of circulating miR-122 in the evaluation of liver function has never been reported. In the present study, changes of serum miRNA levels were first evaluated in acute human hepatotoxicity due to paraquat exposure. Serum samples were collected and analyzed using real-time reverse transcription PCR. The results showed a positive correlation between serum miR-122 and alanine aminotransferase, a clinical biomarker for liver function. Furthermore, serum miR-122 was assessed in patients with hepatitis B and hepatocarcinoma, resulting in distinct miR-122 profiles in these two closely related diseases. In addition to miR-122, another small RNA, U6 small nuclear RNA, was downregulated in hepatocarcinoma patients, suggesting its prognostic significance in this disease. Taken together, these lines of evidence indicate that serum miR-122 may provide a biomarker for diverse liver diseases and, more importantly, suggest that a combination of nucleic acid biomarkers may be used as a sensitive and specific index for discriminating closely related diseases. IntroductionLiver damage, as in the forms of hepatocyte carcinoma, viral hepatitis, acute hepatotoxicity or chronic hepatic injury, is frequently encountered in the practice of medicine. Accumulating knowledge in this field led to the development of a panel of protein-based blood biomarkers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, total protein and albumin. Of these biomarkers, the blood ALT levels are the benchmark for liver function in clinical practice. Although liver malfunction is a common cause of elevated blood ALT levels, other factors impacting on this biomarker cannot be ignored. These effects occur mainly due to its extensive distribution in extrahepatic tissues, such as kidney, heart and skeletal muscle, which compromises its specificity in clinical practice. For example, patients with burns or muscle inflammation also show elevated blood ALT levels (1,2), and approximately one-third of hepatitis C virus (HCV)-infected patients have a normal ALT reading in the blood (3).Distinct from the distribution profile of ALT, a few liverspecific microRNAs (miRNAs), such as miR-122, have recently been characterized (4-6). miRNAs are a type of small endogenous non-coding RNA. Although the biological functions of miRNAs have yet to be elucidated, they are frequently dysregulated in human tumors, and tissue levels of specific miRNAs have been shown to correlate well with the patholo gical development of a variety of cancer types (7,8). Furthermore, the latest finding of miRNA in the blood suggests the potential of miRNA-based blood biomarkers in cancer diagnosis (9,10).A previous study (11), using an acetaminophen-overdose liver injury model, determined miRNA expression profiles in ...
We discuss here a new approach to detecting hepatotoxicity by employing concentration changes of liver-specific blood proteins during disease progression. These proteins are capable of assessing the behaviors of their cognate liver biological networks for toxicity or disease perturbations. Blood biomarkers are highly desirable diagnostics as blood is easily accessible and baths virtually all organs. Fifteen liver-specific blood proteins were identified as markers of acetaminophen (APAP)-induced hepatotoxicity using three proteomic technologies: label-free antibody microarrays, quantitative immunoblotting, and targeted iTRAQ mass spectrometry. Liver-specific blood proteins produced a toxicity signature of eleven elevated and four attenuated blood protein levels. These blood protein perturbations begin to provide a systems view of key mechanistic features of APAP-induced liver injury relating to glutathione and S-adenosyl-L-methionine (SAMe) depletion, mitochondrial dysfunction, and liver responses to the stress. Two markers, elevated membrane-bound catechol-O-methyltransferase (MB-COMT) and attenuated retinol binding protein 4 (RBP4), report hepatic injury significantly earlier than the current gold standard liver biomarker, alanine transaminase (ALT). These biomarkers were perturbed prior to onset of irreversible liver injury. Ideal markers should be applicable for both rodent model studies and human clinical trials. Five of these mouse liver-specific blood markers had human orthologs that were also found to be responsive to human hepatotoxicity. This panel of liver-specific proteins has the potential to effectively identify the early toxicity onset, the nature and extent of liver injury and report on some of the APAP-perturbed liver networks.
Low-cost growth of patterned zinc oxide (ZnO) nanorod arrays (NAs) has attracted much attention with the rapid development of electronics and nanotechnology. Mechanoelectrospinning-assisted continuous hydrothermal synthesis method (MES-CHSM) is proposed to direct-write the precursor patterns for growth of ZnO-NAs, in a digital, low-cost, and mask-free manner. The morphology and distribution of hierarchical ZnO nanorods, having a tremendous impact on gas response, are determined by the process parameters of MES-CHSM. It is highly desirable that the diameter, interval, orientation and distribution of ZnO nanorods can be tuned proactively by changing growth time, solution concentration, the nature of precursor layer, and the pattern by MES. ZnO-NAs exert excellent Ohmic contact with interdigital electrodes when exposure to dry air, NO2 gas and dry air again. The gas response of ZnO sample is surface-reaction-determining. Gas sensing results show highly sensitive and repeatable response-recovery cycles with NO2 gas exposure and the air purge, respectively. The dynamic response of gas sensor shows temperature-dependent response to NO2, even at low concentrations (1-50 ppm). The best gas response is located between 200 ºC and 225 ºC. Gas sensors, prepared by different process parameters, show two laws between the corresponding responses and NO2 concentrations: approximately linear and saturation regions. The optimal process parameters is presented to postpone the occurrence of saturation region, to enlarge measuring range. Please do not adjust marginsPlease do not adjust margins where the MES is an improved electrohydrodynamic direct-writing process with high controllability on the morphology of fibers 32, 33 . This method can achieve highly aligned ZnO nanorods on sub-10micrometer printed patterns, to form hierarchical structures of the highly sensitive sensors. Further, the morphology and distribution of ZnO-NAs are tunable with different process parameters, such as growth time, ZnAc precursor concentration, Zn(NO3)2 concentration in growth solution and the printed micropattern of MES. Their relationships with gas sensing performance are investigated in detail to discover the optimal parameters of process and working. Experimental section PreparationZinc acetate (ZnAc, Zn(CH3COO)22H2O, AR), zinc nitrate (Zn(NO3)2, AR) hydrate and hexamethylenetetramine (HMTA, (CH2)6N4) were purchased from Sinopharm Chemical Reagent Co., Ltd.. Polyethylene oxide (PEO) used in this study was purchased from Aldrich. The relative molecular mass (Mr) of PEO was 600,000. An aqueous solution containing PEO (6wt%) and ZnAc was fabricated by magnetic stirring for 10 hours (h). Aqueous solutions of Zn(NO3)2 (0.2 M) and HMTA (0.2 M) were prepared by magnetic stirring for >0.5 h respectively, then were mixed with equal volume and stirred evenly to fabricated mixed solution of Zn(NO3)2 and HMTA.Interdigitated electrodes of Ag were screen printed on alumina substrate (1 cm*0.8 cm). The distance between adjacent electrodes was 800 µm. Hierarchical...
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