Journal: Antiviral research

Article Title: Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

doi: 10.1016/j.antiviral.2016.08.011

Figure Lengend Snippet: Extended SAA time course and effect of antiviral treatment on SAA levels in BALB/c mice. Mice (n=30) were intranasally infected with mouse-adapted influenza A/California/04/2009 (H1N1)pdm09 virus (1LD90). Control animals (uninfected, n=10) received dilution vehicle (MEM) only. Four hours later, ten mice per group received placebo (saline), oseltamivir at 1 mg/kg/d and 10 mg/kg/d, respectively, twice daily for 5 successive days by oral gavage (+4 hpi, bid × 5). At specific time points (0-7, 14, and 21 dpi), animals were cheek-bled for serum collection. The experiment was terminated 21 days post-virus inoculation. Survival and body weight were monitored daily. (A) Kaplan-Meier survival curves were computed and compared with the log-rank (Mantel-Cox) and Gehan-Wilcoxon test. The hazard ratio was 18.29. (B) Percent body weight change was calculated by dividing the daily body weight by the weight of the same mouse on Day 0. Oseltamivir-treated animals lost significantly less weight at 4-8 dpi compared to placebo animals. (C) Time course of SAA as determined from a single ELISA assay. SAA levels sharply increased at 3 dpi in the placebo group. (D) SAA amounts in serum samples from individual animals taken 3 dpi. Samples were tested in quadruplicates in two independent ELISA assays. Both oseltamivir treatments significantly reduced SAA levels to uninfected control levels. The dashed line in (B) indicates 30% body weight loss. Arrow in (D) points to the only surviving animal from the placebo group with low SAA levels (87 μg/ml). Data are presented as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 compared to placebo.

Article Snippet: SAA was the most promising candidate and was further evaluated in relation to antiviral therapy with oseltamivir phosphate (Tamiflu®), an established, FDA-approved anti-influenza drug.

Techniques: Infection, Enzyme-linked Immunosorbent Assay

Journal: Antiviral research

Article Title: Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

doi: 10.1016/j.antiviral.2016.08.011

Figure Lengend Snippet: SAA levels and systemic cytokine/chemokine profile in BALB/c mice infected with mouse-adapted influenza A/California/04/2009 (H1N1)pdm09 virus (1LD100) and treated with oseltamivir (+4 hpi, 1mg/kg/d, bid × 5). (A) Kaplan-Meier survival curves. The hazard ratio was 14.08. (B) Percent body weight. Oseltamivir-treated animals lost significantly less weight at 2-4 dpi compared to placebo animals. (C) SAA amounts in serum samples at 3 dpi. Oseltamivir treatment significantly reduced SAA levels to uninfected control levels. (D) Proinflammatory cytokines/chemokines in serum samples at 0, 3, and 7 dpi. Note that all placebo animals had died before the end of the experiment. The dashed line in (B) indicates 30% body weight loss. Data are presented as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 compared to placebo.

Article Snippet: SAA was the most promising candidate and was further evaluated in relation to antiviral therapy with oseltamivir phosphate (Tamiflu®), an established, FDA-approved anti-influenza drug.

Techniques: Infection

Journal: Antiviral research

Article Title: Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

doi: 10.1016/j.antiviral.2016.08.011

Figure Lengend Snippet: SAA time course in BALB/c mice infected with influenza A(H3N2) and influenza B virus and effect of antiviral treatment on SAA levels. Mice (n=20) were intranasally infected with (A, B) mouse-adapted influenza A/Victoria/3/75 (H3N2) virus (1LD100) and (C, D) mouse-adapted influenza B/Sichuan/379/99 virus (2LD90), respectively, and treated with oseltamivir (+ 4 hpi, 20 mg/kg/d, bid × 5). At specific time points (0-7 dpi), animals were cheek-bled for serum collection. The experiment was terminated 14 days post-virus inoculation. Survival and body weight were monitored daily (data shown in Supplement Figures S1 and S2). SAA was significantly elevated at 2 and 3 dpi. Data are presented as mean ± SD. **P < 0.01, ****P < 0.0001 compared to placebo; two-way ANOVA with Sidak's multiple comparison test. Oseltamivir treatment reduced mean SAA levels at 3 dpi significantly in (B) P = 0.0195 and (D) P = 0.0036. Unpaired t-test with equal SD.

Article Snippet: SAA was the most promising candidate and was further evaluated in relation to antiviral therapy with oseltamivir phosphate (Tamiflu®), an established, FDA-approved anti-influenza drug.

Techniques: Infection

Journal: Antiviral research

Article Title: Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

doi: 10.1016/j.antiviral.2016.08.011

Figure Lengend Snippet: SAA time course in C57/BL2, Swiss-Webster, and DBA.2 mice infected with influenza A/California/04/09 (H1N1)pdm09 virus and effect of antiviral treatment on SAA levels. Mice (n=20) were intranasally infected (1LD100) and treated with oseltamivir (+ 4 hpi, 20 mg/kg/d, bid × 5). At specific time points (0-7 dpi), animals were cheek-bled for serum collection. The experiment was terminated 14 days post-virus inoculation. Survival and body weight were monitored daily (data shown in Supplement Figures S3-5). SAA peaked at 3dpi. Data are presented as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 compared to placebo; two-way ANOVA with Sidak's multiple comparison test. Oseltamivir treatment reduced mean SAA levels at 3 dpi, but only significantly in (F) P = 0.0056. Unpaired t-test with equal SD.

Article Snippet: SAA was the most promising candidate and was further evaluated in relation to antiviral therapy with oseltamivir phosphate (Tamiflu®), an established, FDA-approved anti-influenza drug.

Techniques: Infection

Journal: Leukemia Research Reports

Article Title: The BH3-mimetic ABT-737 effectively kills acute myeloid leukemia initiating cells

doi: 10.1016/j.lrr.2014.06.001

Figure Lengend Snippet: ABT-737 has a potent cytotoxic effect on bone marrow-derived AML pLSCs. Bone marrow-derived primary AML cells were cultured on a stromal-feeder layer for 24 h and then treated with 30 nM and 300 nM of ABT-737 for 24 h. AML cell viability was evaluated using7-AAD staining and flow cytometry. (A) The cytotoxic effect of ABT-737 on the overall blast population. The graph shows the percentage of live cells for each sample. (B) ABT-737 is equally efficient in eradicating AML pLSCs. The graph shows the percentage of the CD34 + /CD38 − cells within the surviving AML cell population in each sample. E Horizontal lines indicate mean values. Different shapes indicate data-points corresponding to particular patient samples (Patients cross-referencing with : Patient 1 (○), Patient 2 (■), Patient 3 (•), Patient 4 (□)).

Article Snippet: These results, together with previously reported synergistic effects of ABT-737 with chemotherapeutics make BH3-mimetics promising candidates for future AML treatment regimens.

Techniques: Derivative Assay, Cell Culture, Staining, Flow Cytometry

Journal: Leukemia Research Reports

Article Title: The BH3-mimetic ABT-737 effectively kills acute myeloid leukemia initiating cells

doi: 10.1016/j.lrr.2014.06.001

Figure Lengend Snippet: ABT-737 has an equally high cytotoxic efficacy in disseminated AML pLSCs. Bone marrow and peripheral blood-derived primary AML cells from 2 matching patients were cultured and treated and the percentage of surviving cells determined as described before. (A) Viability of bone marrow-derived and peripheral blood-derived overall AML population after exposure to ABT-737. (B) The percentage of CD34 + /CD38 − cells within the surviving population of leukemic blasts in both bone marrow and peripheral blood-derived matching sample sets showing equal efficacy of ABT-737 compound against AML blasts and pLSCs. The % of pLSCs within live AML cell population was evaluated as a number of CD34 + /CD38 − -7AAD − events. Different shapes indicate data-points corresponding to different patient samples. (Patients cross-referencing with : Patient 2 (■), Patient 4 (□)).

Article Snippet: These results, together with previously reported synergistic effects of ABT-737 with chemotherapeutics make BH3-mimetics promising candidates for future AML treatment regimens.

Techniques: Derivative Assay, Cell Culture

Journal: Theranostics

Article Title: Nanoparticle technology for mRNA: Delivery strategy, clinical application and developmental landscape

doi: 10.7150/thno.84291

Figure Lengend Snippet: Summary of on-going clinical studies of mRNA vaccines for infectious disease.

Article Snippet: Several other promising self-amplifying mRNA vaccine candidates are also under development by Arcturus Therapeutics.

Techniques: Vaccines, Virus, Infection, Variant Assay