Effect of chronic valproic Acid treatment on hepatic gene expression profile in wfs1 knockout mouse

Valproic acid (VPA) is a widely used anticonvulsant and mood-stabilizing drug whose use is often associated with drug-induced weight gain. Treatment with VPA has been shown to upregulate Wfs1 expression in vitro. Aim of the present study was to compare the effect of chronic VPA treatment in wild type (WT) and Wfs1 knockout (KO) mice on hepatic gene expression profile. Wild type, Wfs1 heterozygous, and homozygous mice were treated with VPA for three months (300?mg/kg i.p. daily) and gene expression profiles in liver were evaluated using Affymetrix Mouse GeneChip 1.0?ST array. We identified 42 genes affected by Wfs1 genotype, 10 genes regulated by VPA treatment, and 9 genes whose regulation by VPA was dependent on genotype. Among the genes that were regulated differentially by VPA depending on genotype was peroxisome proliferator-activated receptor delta (Ppard), whose expression was upregulated in response to VPA treatment in WT, but not in Wfs1 KO mice. Thus, regulation of Ppard by VPA is dependent on Wfs1 genotype

Koroonaviiruse omikrontüve vastane antikehade kaitse ja T-rakuline immuunvastus pärast BNT162b2-vaktsiini tõhustusdoosi saamist

Eesti Arst 2023; 102(2):11

Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin

Valproic acid (VLP) is a widely used anticonvulsant and mood-stabilizing drug that relieves the endoplasmic reticulum (ER) stress response, a pathogenetic process related to diabetes. The aim of the present study was to evaluate whether acute valproic acid is able to interfere with glucose intolerance in two different diabetes models: The first model was a Wfs1 mutant mouse with an elevated ER stress response and the second model a streptozocin-induced diabetic mouse. VLP (300 mg/kg, i.p.) was administered to Wfs1 knockout (KO) mice and glucose tolerance test was performed 15 min later. VLP did not have an effect on the course of the glucose tolerance test in wild-type mice, while it did normalize the glucose intolerance in Wfs1 knockout mice. Acute valproic acid also lowered the blood glucose levels in streptozocin-treated mice and potentiated the effect of insulin in these mice. Thus, acute valproic acid is effective in lowering blood glucose levels possibly by potentiating insulin action in both Wfs1 KO mice and in streptozocin-induced type 1 diabetic mice

The anti SARS-CoV-2 activity of nanofibrous filter materials activated with metal clusters

Nanofibrous filter materials were prepared by electrospinning a solution of 28 wt% poly(vinylidene fluoride) in N,N-dimethylacetamide with and without the addition of 2 wt% AgNO3, Cu(NO3)2·2.5H2O or ZnCl2. X-ray diffraction, scanning electron microscopy with energy dispersive X-ray spectroscopy, inductively coupled plasma mass spectroscopy, thermogravimetric analysis, contact angle measurement, nitrogen sorption, and mercury intrusion porosimetry methods were used for the characterization of physical structure as well as the chemical composition of the electrospun materials. Particle filtration efficiency and antiviral activity against the SARS-CoV-2 alpha variant were tested in order to estimate the suitability of the prepared electrospun filter materials for application as indoor air filtration systems with virucidal properties. All filter materials prepared with salts demonstrated very high particle filtration efficiency (≥98.0%). The best antiviral activity was demonstrated by a material containing Cu(NO3)2·2.5H2O in the spinning solution, which displayed the decrease in the number of infectious virions by three orders of magnitude after a contact time of 12 h. Materials with the addition of AgNO3 and ZnCl2 decreased the number of infectious virions after the same contact time by only ∼8 and ∼11 times, respectively