Le (2020) Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiellapneumoniae,

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The bacterial pathogen Klebsiella pneumoniae causes urinary tract infections in immunocompromised patients. Generally, the overuse of antibiotics contributes to the potential development and the spread of antibiotic resistance. In fact, certain strains of K. pneumoniae are becoming increasingly resistant to antibiotics, making infection by these strains more difficult to treat. The use of bacteriophages to control pathogens may offer a non-antibiotic-based approach to treat multidrug-resistant (MDR) infections. However, a detailed understanding of phage–host interactions is crucial in order to explore the potential success of phage-therapy for treatment. In this study, we investigated the molecular epidemiology of nine carbapenemase-producing K. pneumoniae isolates from a local hospital in Shanghai, China. All strain isolates belong to sequence type 11 (ST11) and harbor the blaKPC-2 gene. The S1-PFGE (S1 nuclease pulsed field gel electrophoresis) pattern of the isolates did not show any relationship to the multilocus sequence typing (MLST) profiles. In addition, we characterized phage 117 and phage 31 and assessed the potential application of phage therapy in treating K. pneumoniae infections in vitro. The results of morphological and genomic analyses suggested that both phages are affiliated to the T7 virus genus of the Podoviridae family. We also explored phage–host interactions during growth in both planktonic cells and biofilms. The phages’ heterogeneous lytic capacities against K. pneumoniae strains were demonstrated experimentally. Subsequent culture and urine experiments with phage 117 and host Kp36 initially demonstrated a strong lytic activity of the phages. However, rapid regrowth was observed following the initial lysis which suggests that phage resistant mutants were selected in the host populations. Additionally, a phage cocktail (117 + 31) was prepared and investigated for antimicrobial activity. In Luria Broth (LB) cultures, we observed that the cocktail showed significantly higher antimicrobial activity than phage 117 alone, but this was not observed in urine samples. Together, the results demonstrate the potential therapeutic value of phages in treating K. pneumoniae urinary tract infections.

Introduction Liver cancer is one of the most common malignancies across the globe and one of the major causes of cancer-related mortality. With limited available treatment options, there is an urgent need to look for new available options. Genistein is an important plant flavonoid and has been shown to possess tremendous pharmacological potential. The objective of the present study was therefore to evaluate the anticancer effect of the genistein. Material and methods The antiproliferative activity and IC 50 of genistein were determined by MTT assay. Reactive oxygen species (ROS) and cycle distribution were investigated by flow cytometry. Apoptosis was detected by DAPI and annexin V/IP staining. Cell migration was investigated by wound healing assay. Protein expression was estimated by western blotting. Results MTT assay revealed that genistein reduced the cell viability of HepG2 cancer cells in a dose-dependent manner. Genistein also reduced the colony forming potential of the HepG2 cell concentration dependently. The IC 50 of genistein was found to be 25 μM. Genistein caused G2/M cell cycle arrest and G2/M cells increased from 4.2% in the control to 56.4% at 100 μM concentration. Genistein prompted generation of significant ( p < 0.01) amounts of ROS, ultimately favouring cell death. Genistein also triggered apoptosis which was associated with upregulation of cytosolic cytochrome c, Bax, cleaved caspase 3 and 9 expression and downregulation of Bcl-2 expression in HepG2 cells. Conclusions We propose that genistein exhibits significant anticancer activity against liver cancer and therefore may prove beneficial in the management of liver cancer.

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Prostate cancer (PCa) is one of the most common tumors in men and can be lethal, especially if left untreated. A substantial majority of PCa patients not only are diagnosed based on fine needle aspiration (FNA) biopsies, but their treatment choices are also largely driven by the pathological findings obtained with these FNA specimens. It is widely believed that lncRNAs have strong biological significance, but their specific functions and regulatory networks have not been elucidated. LncRNAs may serve as key players and regulators of PCa carcinogenesis and could be novel biomarkers of this cancer. To identify potential markers for early detection of PCa, in this study, we employed a competing endogenous RNA (ceRNA) microarray to identify differentially expressed lncRNAs (DelncRNAs) in PCa tissue and quantitative real-time PCR (qRT-PCR) analysis to validate these DelncRNAs in FNA biopsies. We demonstrated that a total of 451 lncRNAs were differentially expressed in four pairs of PCa/adjacent tissues, and upregulation of the lncRNAs RP11-33A14.1, RP11-423H2.3, and LAMTOR5-AS1 was confirmed in FNA biopsies of PCa by qRT-PCR and was consistent with the ceRNA array data. The association between the expression of the lncRNA LAMTOR5-AS1 and aggressive cancer was also investigated. Regulatory network analysis of DelncRNAs showed that the lncRNAs RP11-33A14.1 and RP11-423H2.3 targeted miR-7, miR-24-3p, and miR-30 and interacted with the RNA binding protein FUS. Knockdown of these DelncRNAs in PCa cells also demonstrated the effects of RP11-423H2.3 on miR-7/miR-24/miR-30 or LAMTOR5-AS1 on miR-942-5p/miR-542-3p via direct interaction. The results of these studies indicate that these three specific lncRNA signatures and regulatory

Multidrug-resistant (MDR) organisms have increased worldwide, posing a major challenge for the clinical management of infection. Bacteriophage is expected as potential effective therapeutic agents for difficult-to-treat infections. When performing bacteriophage therapy, the susceptibility of lytic bacteriophage to the target bacteria is selected by laboratory isolate from patients. The presence of a subpopulation in a main population of tested cells, coupled with the rapid development of phage-resistant populations, will make bacteriophage therapy ineffective. We aimed to treat a man with multifocal urinary tract infections of MDR Klebsiella pneumoniae by phage therapy. However, the presence of polyclonal co-infectious cells in his renal pelvis and bladder led to the failure of three consecutive phage therapies. After analysis, the patient was performed with percutaneous nephrostomy (PCN). A cocktail of bacteriophages was selected for activity against all 21 heterogeneous isolates and irrigated simultaneously via the kidney and bladder to eradicate multifocal colonization, combined with antibiotic treatment. Finally, the patient recovered with an obviously improved bladder. The success of this case provides valuable treatment ideas and solutions for phage treatment of complex infections.Clinical Trial Registrationwww.chictr.org.cn, identifier ChiCTR1900020989.