Significance: Type I interferons (IFN-I) exhibit various biological effects during viral infections, and they have been successfully used for clinical treatment of viral diseases. Humans express 12 IFNα subtypes, which strongly differ in their antiviral responses against different viruses. Here we analyzed the antiviral activity of all human IFNα subtypes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to identify the underlying immune signatures and explore their therapeutic potential. Our data provide a systemic pattern of antiviral host effector responses mediated by high antiviral IFN-I, which could help to identify key cellular effectors targeted in novel therapeutic approaches against SARS-CoV-2 infection.

Parenteral amphotericin B has been considered as first-line therapy in the treatment of systemic fungal and parasitic infections, however its use has been associated with a number of limitations including affordability, accessibility, and an array of systemic toxicities. Until very recently, it has been very challenging to develop a bioavailable formulation of amphotericin B due to its physical chemical properties, limited water and lipid solubility, and poor absorption. This perspective reviews several novel oral Amphotericin B formulations under development that are attempting to overcome these limitations.

Evidence from the literature suggests that dietary flaxseed lignans have the ability to modulate inflammation, which is recognized as the underlying basis of multiple chronic human diseases in older adults. Our objective was to determine the effects of oral lignan supplementation on biochemical and functional indicators of inflammation as well as safety and tolerability in older healthy adults. We designed a randomized, double-blind, placebo-controlled clinical trial in older healthy adults (60–80 years) to assess flaxseed lignan–enriched complex (∼38% secoisolariciresinol diglucoside [SDG]; 600 mg SDG dose) oral supplementation effects on biochemical and functional indicators of inflammation and safety and tolerability in older healthy adults after 6 months of once-daily oral administration. The clinical trial confirmed that plasma concentration of total flaxseed lignans (free and conjugated forms) secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (ENL) were significantly associated with daily oral supplementation of flaxseed lignan–enriched complex (p < 0.05). A significant decrease in systolic blood pressure (SBP; from a mean of 155 ± 13 mm Hg at baseline to 140 ± 11 mm Hg at 24 weeks) was observed in lignan-supplemented participants stratified into an SBP ≥140 mm Hg subcategory (p = 0.04). No differences were found between treatment or placebo groups in terms of cognition, pain, activity, physical measurements (calf, waist, and upper arm circumstances), and grip strength. With respect to blood inflammatory markers, lipid profiles, and biochemical parameters, no significant differences were found between treatment and placebo groups at the end of the 6-month supplementation. No adverse effects were reported during supplementation. These data further support the safety and tolerability of long-term flaxseed lignan–enriched complex supplementation in older adults and identify an ability to favorably modulate SBP, an important risk factor in cardiovascular disease.

Systemic cytotoxic chemotherapy remains the mainstay of metastatic breast cancer; however, prognosis and overall survival is unfavorable due to inadequate treatment response and/or unacceptable toxicity. Natural compounds and their active metabolites receive increasing attention as possible adjuvant therapy with cancer chemotherapeutics to improve treatment response, survival rates, and quality of life of breast cancer patients. This study investigated the combination of flaxseed lignans (Secoisolariciresinol and Enterolactone) with classic chemotherapeutic agents (Docetaxel, Doxorubicin, and Carboplatin) with different mechanisms of action to determine whether flaxseed lignans could enhance the cytotoxic effect of such drugs in the metastatic breast cancer cell lines, SKBR3 and MDA-MB-231. The experimental data suggests that flaxseed lignans significantly enhanced the ability of chemotherapeutic agents to cause cytotoxicity in SKBR3 and MDA-MB-231 breast cancer cells. A three compound combination study found that enterolactone and metformin together in combination with relatively low concentrations of chemotherapeutic drugs were able to significantly decrease cancer cell viability, compared to low concentrations of the individual chemotherapeutic drug alone. Our in vitro evaluation suggests a future direction in improving chemotherapeutic efficacy in breast cancer by adjuvant therapy with the flaxseed lignans.

Increased oxidative stress and inflammation are associated with aging, and contribute to an increased risk of chronic disease in older adults. Flaxseed lignans demonstrate antioxidant and anti-inflammatory activity, but their ability to reduce oxidative stress and inflammation markers in older adult populations has received limited investigation. This is a chronic intervention trial of community-dwelling healthy older adults to examine the effects of a flaxseed lignan (secoisolariciresinol diglucoside; SDG) enriched supplement (BeneFlax) compared to a placebo. The primary aim was to demonstrate the safety of BeneFlax and confirm its anti-inflammatory efficacy on markers of oxidative stress and inflammation, and subsequent functional outcomes, including those associated with its anti-inflammatory efficacy. A secondary aim was to determine flaxseed lignan metabolite concentrations in blood. A double-blind randomized clinical trial was conducted. Subjects were healthy community-dwelling adults aged 60-80 years. Testing was performed at baseline, 8, 16, and 24 weeks. The 24-week intervention consisted of 600 milligrams (mg) of SDG daily or an equivalent amount (volume) of placebo. All participants received 1000 international units of vitamin D to ensure adequate vitamin D status. Measurements consisted of blood pressure, hematology, and tolerability for safety assessments; blood oxidative stress and inflammatory biomarkers for efficacy; and cognition, muscle strength, and pain as functional outcomes. Secondary endpoints of plasma levels of lignan metabolites were analyzed by mass spectrometry. Other tests, such as bone turnover markers and fecal levels of flax cyclolinopeptides, will be performed at a later date. Thirty-two participants were recruited (19 intervention and 13 control) and all completed the trial. Numerous Health Canada-imposed exclusion criteria limited recruitment success. Analyses are ongoing, but the baseline data available for a number of parameters indicate no differences between treatment groups. Safety measures (vital signs) did not change from baseline and were not significantly different between treatment and placebo groups at 24 weeks. Preliminary results indicate that no safety concerns are associated with administering 600 mg SDG for 24 weeks to adults between the ages of 60 and 80 years. Clinicaltrials.gov NCT01846117; https://clinicaltrials.gov/ct2/show/NCT01846117 (Archived by WebCite at http://www.webcitation.org/6nlDZNjmA).

Purpose: CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio, for the treatment of acute myeloid leukemia. The Scavenger Receptor class B type I (SR-BI) plays an important role in mediating the uptake of high-density lipoproteins. The purpose of this study is to assess the role of the cell surface lipoprotein receptor SR-BI in the uptake of CPX-351 liposomes (Jazz Pharmaceuticals) into K562 leukemia cells. Methods: K562 cells were pre-treated with 10 nM siRNA for 48 h and then treated with varying amount of CPX-351 for 24, 48 and 72 h. Cells were then collected and analyzed at 480/590 nm on a CytoFLEX Multicolour flow instrument to determine cellular uptake of daunorubicin. Experimental data were analyzed using two-way ANOVA with Bonferroni multiple comparisons. Significance was set at p < .05. Results: K562 cells pre-treated with SR-BI siRNA for 48 h had a reduced SRB1 cell surface concentration (74–85%). Addition of CPX-351 at 10–50 nM followed by measurement of cellular daunorubicin at 48, 48 or 72 h showed a significantly lower percentage of daunorubicin positive population compared with control K562 cells (p < .05). There was significantly less daunorubicin taken up in the SR-BI knock-down cells across all drug concentrations and at all three time points, although there were no concentration-related trends. Conclusions: These preliminary studies suggest that SR-BI may be one potential mechanism by which CPX-351 is taken up into K562 cells.