Decoding the mechanism governing the structural stability of wheat germ agglutinin and its isolated domains: A combined calorimetric, NMR, and MD simulation study.

Wheat germ agglutinin (WGA) demonstrates potential as an oral delivery agent owing to its selective binding to carbohydrates and its capacity to traverse biological membranes. In this study, we employed differential scanning calorimetry and molecular dynamics simulations to comprehensively characterize the thermal unfolding process of both the complete lectin and its four isolated domains. Furthermore, we present the nuclear magnetic resonance structures of three domains that were previously lacking experimental structures in their isolated forms. Our results provide a collective understanding of the energetic and structural factors governing the intricate unfolding mechanism of the complete agglutinin, shedding light on the specific role played by each domain in this process. The analysis revealed negligible interdomain cooperativity, highlighting instead significant coupling between dimer dissociation and the unfolding of the more labile domains. By comparing the dominant interactions, we rationalized the stability differences among the domains. Understanding the structural stability of WGA opens avenues for enhanced drug delivery strategies, underscoring its potential as a promising carrier throughout the gastrointestinal environment.

Novel Blocker of Onco SK3 Channels Derived from Scorpion Toxin Tamapin and Active against Migration of Cancer Cells.

Peptide-based therapy against cancer is a field of great interest for biomedical developments. Since it was shown that SK3 channels promote cancer cell migration and metastatic development, we started using these channels as targets for the development of antimetastatic drugs. Particularly, tamapin (a peptide found in the venom of the scorpion Mesobuthus tamulus) is the most specific toxin against the SK2 channel currently known. Considering this fact, we designed diverse tamapin mutants based on three different hypotheses to discover a new potent molecule to block SK3 channels. We performed in vitro studies to evaluate this new toxin derivative inhibitor of cancer cell migration. Our results can be used to generate a new tamapin-based therapy against cancer cells that express SK3 channels.

Management and Systemic Implications of Diabetic Neovascular Glaucoma.

OBJECTIVES: To study the efficacy and safety of different treatments for diabetic neovascular glaucoma (NVG). We additionally attempt to determine if the presence of NVG could be a predictor of cardiovascular disease or death. METHOD: This is a retrospective, observational cohort study including patients diagnosed with diabetic NVG from 2006 to 2016 at the Hospital Clínico Universitario de Valladolid (Spain). Extracted data included clinical characteristics of the patients, glycated haemoglobin levels, and ocular treatment. Visual acuity (VA), intraocular pressure (IOP), cardiovascular events, and deaths were registered. RESULTS: 30 eyes from 23 patients were followed for a mean of 4.48 years (SD = 2.82 years). The IOP-lowering intervention groups were: Ahmed implant (11 eyes), laser cyclo-photocoagulation (CPC; 6 eyes), both (4 eyes), or none (9 eyes). IOP success was achieved in 100% of the eyes with Ahmed and/or laser CPC and in 44.4% of the eyes with no IOP-lowering procedure (p= 0.002). Most eyes with Ahmed implant (with or without CPC) maintained or improved their VA (100 and 63.6%, respectively). 33.3% of the eyes with laser CPC and 25% of those with no IOP-lowering intervention maintained or improved their VA (p = 0.028). Hypotony was the only adverse effect (after laser CPC). No statistically significant difference could be established between low VA (finger count or worse), poor IOP control, or bad metabolic control and mortality or cardiovascular event (p > 0.05), however, the four patients who died had poor VA at the time of NVG diagnosis. CONCLUSIONS: Ahmed implant surgery is a safe and effective treatment option for diabetic NVG. Medical treatment alone is not the best option for most cases. Advanced NVG could be an indicator of higher mortality risk in diabetic patients.