Background: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. Materials and Methods: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Results: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p < 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p < 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p > 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p < 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.05) in diabetic mice compared to vehicle control. Conclusions: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.

Background: Inflammation in cystic fibrosis (CF) airways is difficult to treat with well-established regimens often including azithromycin (AZ) as an immunomodulatory drug. As AZ has been reported to require CF transmembrane conductance regulator (CFTR) to be able to reduce interleukin (IL)-8 and given the emergence of highly effective CFTR “triple” modulator therapy (elexacaftor/tezacaftor/ivacaftor; ETI), the aim of this study was to investigate the effect of AZ and ETI, singly and in combination, on ion channel activity and to assess the potential anti-inflammatory effects.Methods: Electrophysiological assessment of ETI and AZ was performed on three-dimensional cultures of primary CF human bronchial epithelial (HBE) cells using a Multi Trans-Epithelial Current Clamp. IL-8 from NuLi-1 (non-CF) and CuFi-1 (CF) cells treated with AZ was measured by ELISA. Inflammatory mediators from primary CF HBE cells exposed to tumour necrosis factor-α in the presence of AZ, ETI and their combination, were screened using the Proteome Profiler™ Human Cytokine Array Kit, with selected targets validated by ELISA.Results: AZ did not alter CFTR chloride efflux, nor did it have any synergistic/antagonistic effect in combination with ETI. AZ reduced IL-8 in NuLi-1 but not CuFi-1 cells. The Proteome Profiler™ screen identified several disease-relevant cytokines that were modulated by treatment. Subsequent analysis by ELISA showed IL-8, IL-6, CXCL1 and granulocyte–macrophage colony-stimulating factor to be significantly reduced by treatment with ETI, but not by AZ.Conclusions: Incorporating ETI into the standard of CF care provides an opportunity to re-evaluate therapeutic regimens to reduce treatment burden and safely discontinue chronic treatments such as AZ, without loss of clinical benefit. Identification of redundant treatments in the era of CFTR modulation may improve medication adherence and overcome potential adverse effects associated with the chronic use AZ and other drugs.

Background/Objectives: Hydrogels infused with silver nanoparticles (AgNPs) are widely used for their antibacterial properties, yet their stability, specifically upon contact with solid growth media (agar), remains poorly explored. This study compared two hydrogel matrices, anionic Carbopol 934 and non-ionic Pluronic F127, incorporating AgNPs of three different sizes. The evaluation focused on colloidal stability and antibacterial efficacy against Gram-positive and Gram-negative bacteria. Methods: In this study AgNPs (~20, ~55, and ~65 nm) were synthesised via a wet-chemical method and characterised by UV–visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). AgNPs were incorporated into Carbopol 934 and Pluronic F127 hydrogel matrices. Colloidal stability was monitored over four months of storage and upon contact with tryptic soy agar (TSA). Antibacterial activity was assessed using agar diffusion assays. Results: Showed that both hydrogel systems maintained AgNP stability during storage, comparable to aqueous suspensions. However, upon contact with TSA, aggregation of Carbopol–AgNP hydrogels occurred, whereas Pluronic–AgNP hydrogels remained stable. In antibacterial assays, both hydrogels produced larger zones of inhibition (ZOI) than AgNP suspensions against Gram-negative bacteria (E. coli, P. aeruginosa), with Carbopol–AgNP hydrogels demonstrating superior efficacy in an inverse size-dependent manner. Against Gram-positive bacteria (S. aureus, S. epidermidis), Pluronic–AgNP hydrogels initially showed larger ZOIs due to the polymer’s intrinsic antibacterial activity. However, after correcting for this baseline, Carbopol–AgNP hydrogels exhibited superior net efficacy, with S. epidermidis showing greater susceptibility than S. aureus. Conclusions: While both Carbopol 934 and Pluronic F127 stabilise AgNPs during storage, the matrix type significantly influences behaviour at the biological interface. Carbopol–AgNP hydrogels aggregate upon contact with solid agar yet deliver superior, size-dependent antibacterial activity compared to the stable but less potent Pluronic systems.