Journal: Pharmaceuticals

Article Title: New Assay Systems to Characterize the Broad-Spectrum Antiherpesviral and Non-Herpesviral Activity of Cyclin-Dependent Kinase (CDK) 8 Inhibitors

doi: 10.3390/ph18101560

Figure Lengend Snippet: Determination of anti-EBV activity in lytic assay system with TPA-induced P3HR-1 cells. ( A ) Schematic overview of the antiviral assay designed to assess compound activity against EBV. ( B ) CDK8 inhibitors (BI-1347, CCT-251921, MSC-2530818) were tested for cytotoxicity using a Neutral Red uptake assay (orange line) and for antiviral efficacy by qPCR (black line). Cell viability and viral replication are expressed as percentages relative to DMSO-treated controls. ( C ) The reference compounds, adefovir dipivoxil (ADV), adefovir (AFV), and tenofovir alafenamide (TAF), were evaluated for their cytotoxic effects (orange lines) and for antiviral activity (black lines). Data represent mean ± SD of three replicates normalized to DMSO controls. ( D ) Summary of EC 50 , CC 50 , and selectivity index (SI) values for CDK8 inhibitors and reference compounds based on a minimum of two independent experiments.

Article Snippet: BI-1347, CCT-251921, MSC-2530818 targeting CDK8, adefovir (AFV), brincidofovir (BCV), cidofovir (CDV), EIDD-1931, ganciclovir (GCV), tenofovir alafenamide (TFA), and tenofovir disoproxil (TDP) as reference compounds were obtained from MedChemExpress, Monmouth Junction, NJ, USA.

Techniques: Activity Assay, Antiviral Assay

Journal: Biomedicines

Article Title: SARS-CoV-2 RdRp Inhibitors Selected from a Cell-Based SARS-CoV-2 RdRp Activity Assay System

doi: 10.3390/biomedicines9080996

Figure Lengend Snippet: IC 50 and inhibition percentage of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) activity at the maximum concentrations. It was representative of at least three independent experiments. The data were presented as mean ± standard error of the mean.

Article Snippet: Additionally, nucleoside or nucleotide analogs adefovir dipivoxil (PubChem CID: 60871), emtricitabine (PubChem CID: 60877), telbivudine (PubChem CID: 159269), entecavir hydrate (PubChem CID: 135526609), moroxydine HCl (PubChem CID: 76621) and rifampin (PubChem CID: 135398735) (Selleckchem, Pittsburgh, PA, USA) were procured; the10 mM stock solution of each analog in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) was stored at −80 °C.

Techniques: Inhibition, Activity Assay

Journal: Biomedicines

Article Title: SARS-CoV-2 RdRp Inhibitors Selected from a Cell-Based SARS-CoV-2 RdRp Activity Assay System

doi: 10.3390/biomedicines9080996

Figure Lengend Snippet: Effect of nucleoside and nucleotide analogs on SARS-CoV-2 RdRp activity. HEK293T cells were transfected with p(+)FLuc-(−)UTR-NLuc and pCI-SARS2-nsp12N. After 6 h, the cells were treated with serially diluted-adefovird dipivoxil ( A ), emtricitabine ( B ), telbivudine ( C ), entecavir hydrate ( D ), moroxydine HCl ( E ), or rifampin ( F ) for 15 h. FLuc and NLuc activities were measured to determine the NLuc/FLuc ratios. Statistical comparisons were conducted using one-way analysis of variance (ANOVA) followed by Bonferroni’s multiple comparison test. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001 vs. 0 μM (upper graph). The IC 50 values were calculated using non-linear regression analysis (lower graph). The data were representative of at least three independent experiments and presented as mean ± standard error of the mean.

Article Snippet: Additionally, nucleoside or nucleotide analogs adefovir dipivoxil (PubChem CID: 60871), emtricitabine (PubChem CID: 60877), telbivudine (PubChem CID: 159269), entecavir hydrate (PubChem CID: 135526609), moroxydine HCl (PubChem CID: 76621) and rifampin (PubChem CID: 135398735) (Selleckchem, Pittsburgh, PA, USA) were procured; the10 mM stock solution of each analog in dimethyl sulfoxide (Sigma-Aldrich, Burlington, MA, USA) was stored at −80 °C.

Techniques: Activity Assay, Transfection, Comparison

Journal: Viruses

Article Title: Development of a Novel Human Hepatoma Cell Line Supporting the Replication of a Recombinant HBV Genome with a Reporter Gene

doi: 10.3390/v18020187

Figure Lengend Snippet: Evaluation of long-term HiBiT activity and sensitivity to nucleos(t)ide analogs in HepG2-B4 cells. ( a ) Time course of extracellular HiBiT activity in HepG2-B4 cells seeded at different densities (1 × 10 4 , 7.5 × 10 3 , or 5 × 10 3 cells/well) and maintained in 2% DMSO. Culture supernatants were replaced every 2–4 days, and HiBiT activity (LU/mL) was measured up to 42 days. Values are shown as the mean ± standard deviation of experiments performed using two wells per condition. ( b ) The upper graph shows the effect of various concentrations of nucleos(t)ide analogs (ETV, TDF, TAF, ADV) on extracellular HiBiT activity in HepG2-B4 cells. Cells were maintained in medium containing 2% DMSO or the indicated drug concentrations, and HiBiT activity was measured after 25 days. Results are shown as percentages relative to the DMSO (2%) control group (set at 100%). The lower graph shows the cell viability of nucleos(t)ide analogs in HepG2-B4 cells, assessed by the Cell Counting Kit-8 (CCK-8) according to the manufacturer’s instructions. Cells were treated as described in the upper panel. Cell viability was evaluated on day 25. Results are shown as percentages relative to the DMSO (2%) control group (set at 100%) and represent the mean ± standard deviation of experiments performed using three wells per condition. Abbreviations: ADV, adefovir; ETV, entecavir; TAF, tenofovir alafenamide fumarate; TDF, tenofovir disoproxil fumarate.

Article Snippet: Entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), and adefovir (ADV) were purchased from Selleck Chemicals (Houston, TX, USA) and dissolved in DMSO.

Techniques: Activity Assay, Standard Deviation, Control, Cell Counting, CCK-8 Assay

Journal: Frontiers in Aging

Article Title: Evidence that C/EBP-β LAP Increases Fat Metabolism and Protects Against Diet-Induced Obesity in Response to mTOR Inhibition

doi: 10.3389/fragi.2021.738512

Figure Lengend Snippet: Adefovir dipivoxil prevents diet-induced obesity in mice. Percent weight change in mice fed either LFD or HFD and treated with increasing concentrations of adefovir dipivoxil (ADV) in the chow (A) or by intraperitoneal injection (B) Percent fat mass change in mice fed either LFD or HFD and treated with increasing concentrations of adefovir dipivoxil (ADV) in the chow (C) or by intraperitoneal injection (D) Circles: individual animals, bars: average + - standard deviation. *: p < 0.05 vs LFD control, **: p < 0.01 vs LFD control, +: p < 0.05 vs HFD control, ++: p < 0.01 vs HFD control.

Article Snippet: Animals were fed either Research Diet D12492 (HFD) or D12450j (LFD) (Research Diets, New Brunswick NJ) and treated with daily intraperitoneal injections of 8 mg/kg rapamycin (LC Laboratories, Woburn MA) (cohort 1 and 2), daily intraperitoneal injections of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, or 25 mg/kg adefovir dipivoxil (cohorts 2 and 3) (Carbosynth, UK), or with adefovir dipivoxil mixed in the chow for 6 weeks at 21 mg/kg, 42 mg/kg, 84 mg/kg, or 210 mg/kg w/w (cohorts 2 and 3).

Techniques: Injection, Standard Deviation, Control

Journal: Frontiers in Aging

Article Title: Evidence that C/EBP-β LAP Increases Fat Metabolism and Protects Against Diet-Induced Obesity in Response to mTOR Inhibition

doi: 10.3389/fragi.2021.738512

Figure Lengend Snippet: Adefovir dipivoxil increases expression of C/EBP-β LAP and EDIL3. (A) Representative western blot image against EDIL3, C/EBP-β (LAP and LIP isoforms) and GAPDH. (B–E) Densitometric analysis of the western blot in panel (A) Circles: individual animals, bars: average + - standard deviation. *: p < 0.05 vs LFD control, **: p < 0.01 vs LFD control, +: p < 0.05 vs HFD control, ++: p < 0.01 vs HFD control.

Article Snippet: Animals were fed either Research Diet D12492 (HFD) or D12450j (LFD) (Research Diets, New Brunswick NJ) and treated with daily intraperitoneal injections of 8 mg/kg rapamycin (LC Laboratories, Woburn MA) (cohort 1 and 2), daily intraperitoneal injections of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, or 25 mg/kg adefovir dipivoxil (cohorts 2 and 3) (Carbosynth, UK), or with adefovir dipivoxil mixed in the chow for 6 weeks at 21 mg/kg, 42 mg/kg, 84 mg/kg, or 210 mg/kg w/w (cohorts 2 and 3).

Techniques: Expressing, Western Blot, Standard Deviation, Control

Journal: Frontiers in Aging

Article Title: Evidence that C/EBP-β LAP Increases Fat Metabolism and Protects Against Diet-Induced Obesity in Response to mTOR Inhibition

doi: 10.3389/fragi.2021.738512

Figure Lengend Snippet: Anti-obesogenic effects of adefovir dipivoxil in mice. Percent weight change in mice fed either LFD or HFD and treated with 210 mg/kg adefovir dipivoxil (ADV) in the chow (A) or by intraperitoneal injection of 10 mg/kg/day ADV (B) Percent fat mass change in mice fed either LFD or HFD and treated with 210 mg/kg adefovir dipivoxil (ADV) in the chow (C) or by intraperitoneal injection of 10 mg/kg/day ADV (D) Circles: individual animals, bars: average + - standard deviation. *: p < 0.05 vs LFD control, **: p < 0.01 vs LFD control, +: p < 0.05 vs HFD control, ++: p < 0.01 vs HFD control.

Article Snippet: Animals were fed either Research Diet D12492 (HFD) or D12450j (LFD) (Research Diets, New Brunswick NJ) and treated with daily intraperitoneal injections of 8 mg/kg rapamycin (LC Laboratories, Woburn MA) (cohort 1 and 2), daily intraperitoneal injections of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, or 25 mg/kg adefovir dipivoxil (cohorts 2 and 3) (Carbosynth, UK), or with adefovir dipivoxil mixed in the chow for 6 weeks at 21 mg/kg, 42 mg/kg, 84 mg/kg, or 210 mg/kg w/w (cohorts 2 and 3).

Techniques: Injection, Standard Deviation, Control

Journal: Frontiers in Aging

Article Title: Evidence that C/EBP-β LAP Increases Fat Metabolism and Protects Against Diet-Induced Obesity in Response to mTOR Inhibition

doi: 10.3389/fragi.2021.738512

Figure Lengend Snippet: Adefovir dipivoxil promotes the expression of fatty acid oxidation genes. (A) Representative western blot image against C/EBP-β (LAP and LIP isoforms), ACSL1, CPT-1A, and GAPDH. (B–F) Densitometric analysis of the western blot in panel (A) Relative Quantity, as measured via RT-PCR, for VLCAD (G) , LCAD (H) , MCAD (I) , and SCAD (J) Circles: individual animals, bars: average + - standard deviation. *: p < 0.05 vs LFD control, **: p < 0.01 vs LFD control, +: p < 0.05 vs HFD control, ++: p < 0.01 vs HFD control.

Article Snippet: Animals were fed either Research Diet D12492 (HFD) or D12450j (LFD) (Research Diets, New Brunswick NJ) and treated with daily intraperitoneal injections of 8 mg/kg rapamycin (LC Laboratories, Woburn MA) (cohort 1 and 2), daily intraperitoneal injections of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, or 25 mg/kg adefovir dipivoxil (cohorts 2 and 3) (Carbosynth, UK), or with adefovir dipivoxil mixed in the chow for 6 weeks at 21 mg/kg, 42 mg/kg, 84 mg/kg, or 210 mg/kg w/w (cohorts 2 and 3).

Techniques: Expressing, Western Blot, Reverse Transcription Polymerase Chain Reaction, Standard Deviation, Control

Journal: Frontiers in Aging

Article Title: Evidence that C/EBP-β LAP Increases Fat Metabolism and Protects Against Diet-Induced Obesity in Response to mTOR Inhibition

doi: 10.3389/fragi.2021.738512

Figure Lengend Snippet: C/EBP-β LAP is a druggable target to increase fat catabolism. Two pharmacological interventions, rapamycin and adefovir dipivoxil, converge on C/EBP-β LAP to enhance fatty acid oxidation and increase fatty acid catabolism, thereby protecting against obesogenic diets. Rapamycin increases the relative expression of C/EBP-β LAP by increasing its translation, while adefovir dipivoxil is acting through a yet to be determined mechanism.

Article Snippet: Animals were fed either Research Diet D12492 (HFD) or D12450j (LFD) (Research Diets, New Brunswick NJ) and treated with daily intraperitoneal injections of 8 mg/kg rapamycin (LC Laboratories, Woburn MA) (cohort 1 and 2), daily intraperitoneal injections of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, or 25 mg/kg adefovir dipivoxil (cohorts 2 and 3) (Carbosynth, UK), or with adefovir dipivoxil mixed in the chow for 6 weeks at 21 mg/kg, 42 mg/kg, 84 mg/kg, or 210 mg/kg w/w (cohorts 2 and 3).

Techniques: Expressing

Journal: International Journal of Hepatology

Article Title: A Seven-Year Retrospective Study on the Surveillance of Hepatitis B in Laos

doi: 10.1155/2018/9462475

Figure Lengend Snippet: Type of drugs, number, and % on total and dual treatments.

Article Snippet: Pegasys + Adefovir , 2 , 0.3% , 1.6%.

Techniques:

Journal: International Journal of Hepatology

Article Title: A Seven-Year Retrospective Study on the Surveillance of Hepatitis B in Laos

doi: 10.1155/2018/9462475

Figure Lengend Snippet: Type of drugs, number, and % on total and triple treatments.

Article Snippet: Pegasys + Adefovir , 2 , 0.3% , 1.6%.

Techniques: