Priya Jain

Ionic transport through nanofluidic systems is a problem of fundamental interest in transport physics and has broad relevance in desalination, fuel cells, batteries, filtration, and drug delivery. When the dimension of the fluidic system approaches the size of molecules in solution, fluid properties are not homogeneous and a departure in behavior is observed with respect to continuum-based theories. Here we present a systematic study of the transport of charged and neutral small molecules in an ideal nanofluidic platform with precise channels from the sub-microscale to the ultra-nanoscale (<5 nm). Surprisingly, we find that diffusive transport of nano-confined neutral molecules matches that of charged molecules, as though the former carry an effective charge. Further, approaching the ultra-nanoscale molecular diffusivities suddenly drop by up to an order of magnitude for all molecules, irrespective of their electric charge. New theoretical investigations will be required to shed light onto these intriguing results.

Agathisflavone is a bioactive compound in Anacardium occidentale . In this study, we investigated inhibition neuroinflammation in BV2 microglia by agathisflavone. Neuroprotective activity of the compound was investigated in differentiated SH‐SY5Y cells. Experiments in lipopolysaccharide (LPS)‐activated BV2 microglia showed that pretreatment with agathisflavone (5–20 μM) produced significant reduction in the release of tumour necrosis factor‐α, interleukin‐6, interleukin‐1β, NO, and PGE 2 from the cells. Immunoblotting experiments also revealed that agathisflavone reduced levels of iNOS and COX‐2 protein. Further studies revealed that agathisflavone reduced neuroinflammation by targeting critical steps in NF‐κB signalling in BV2 microglia. Treatment of SH‐SY5Y cells with conditioned medium from LPS‐activated BV2 microglia produced a significant reduction in neuronal viability. However, conditioned medium from BV2 cells that were stimulated with LPS in the presence of agathisflavone did not induce neurotoxicity. Agathisflavone also produced neuroprotection in APPSwe plasmid‐transfected SH‐SY5Y neurons. The compound further attenuated LPS‐induced and APPSwe plasmid‐induced reduction in SIRT1 in BV2 microglia and SH‐SY5Y, respectively. In the presence of EX527, agathisflavone lost its anti‐inflammatory and neuroprotective activities. Our results suggest that agathisflavone inhibits neuroinflammation in BV2 microglia by targeting NF‐κB signalling pathway. The compound also reduces neurotoxicity through mechanisms that are possibly linked to SIRT1 in the microglia and neurons.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor-α monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils. OBJECTIVES: To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment. METHODS: The 24-week, randomized, double-blind, placebo-controlled, phase IIb portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomized to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in Itch Severity Score (ISS)7 at week 12. The key secondary endpoint was change from baseline in Urticaria Activity Score (UAS)7 at week 12. Additional secondary endpoints included other metrics to assess CSU at week 24, blood eosinophil levels, and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups. RESULTS: Of 155 patients, 59 were randomized to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at week 12 between benralizumab and placebo [benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval (CI) -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% CI -4.09 to 0.50] nor in change from baseline in UAS7 score at week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.407; benralizumab 60 mg vs. placebo, P = 0.082). Depletion of blood eosinophil levels was observed at week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab. CONCLUSIONS: Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.