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Surface topological differences of phage infected uropathogenic Escherichia coli (UPEC) strains, revealed by atomic force microscopy

BackgroundAtomic force microscopy (AFM) is an advance microscopic technique that provides three dimensional structures of cell surfaces with high resolution. In the present study AFM was used for comparative analysis of surface topology of phage infected and uninfected Uropathogenic Escherichia coli (UPEC) cells. Two UPEC strains NE and HN were isolated from urine samples of Urinary tract infection patients and their specific narrow host range lytic phages 3S and HNΦ were isolated from the sewage of different areas.ResultsOn the basis of one step growth curve both phages characterized as short latent period phages with latency period of about 30 min. On AFM analysis significant difference in topology of healthy and infected cells were observed. It was hypothesized that progeny of both lytic phages released out from their respective host cells in different manner. The image of 3S infected UPEC host cells (NE) revealed multiple internal projections which showed progeny phages released out from host cells through these multiple sites. Whereas images of HNΦ infected HN host cells showed central depression which illustrated that new phages released out through single exit point from the middle of cell.ConclusionsThese results are significant to extend future studies on isolated phages as an effective tool for phage therapy.

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Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy

BackgroundChemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among published guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assessed the efficacy and safety of triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy comprising palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication [complete response (CR)] in the acute phase (0–24 h), late phase (24–168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication [complete control (CC)].ResultsPrevalence of a CR during the acute phase, delayed phase, and overall was 100, 91.9 and 91.9%, whereas that of CC was 100, 84.4 and 84.4%, respectively. The most common adverse event was mild constipation; severe adverse events related to antiemetic treatment were not observed.ConclusionTriple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in the prevention of CINV in patients receiving a carboplatin-containing regimen.

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The effects for PM2.5 exposure on non-small-cell lung cancer induced motility and proliferation

BackgroundIncreasing urbanization and associated air pollution, including elevated levels of particulate matter (PM), are strongly correlated with the development of various respiratory diseases. In particular, PM2.5 has been implicated in promoting lung cancer initiation, growth and progression. Cell migration and proliferation are crucial for the progression of cancer. However, the molecular signatures and biological networks representing the distinct and shared features of non-small cell lung cancer (NSCLC) after PM2.5 exposure are unknown.ResultsFunctional assays demonstrated higher proliferation, migration and invasion of cancer cells stimulated with PM2.5. To investigate the complicated mechanisms, we performed global transcriptome profiling of the A549 cell line. Particularly, transcriptome sequencing revealed invasive characteristics reminiscent of cancer cells. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining the invasive and proliferative properties of PM2.5-exposed cells, respectively. Interestingly, under the PM2.5-stimulated condition, the A549 and H1299 cells strengthened obviously properties in motility and proliferation. Based on the network model reconstructing the shared protein–protein interactions, we selected the two most up-regulated genes, interleukin-1β (IL1β) and matrix metalloprotease 1 (MMP1), as key regulators responsible for the effects of PM2.5 exposure. Notably, IL1β and MMP1 expression was elevated in independent assays, which was further enhanced by PM2.5.ConclusionTaken together, our systems approach to investigating PM2.5 exposure provides a basis to identify key regulators responsible for the pathological features of NSCLC.

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