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ACS Nano ; 14(9): 11787-11798, 2020 09 22.
Article in English | MEDLINE | ID: covidwho-889132


The COVID-19 pandemic has become a major worldwide crisis. Although respiratory symptoms are a key feature of the disease, many people who are hospitalized with COVID-19 also suffer acute kidney injury, a condition that exacerbates patient mortality and may have to be treated through renal replacement therapy. Much of the focus on hospital capacity during the pandemic has centered on the availability of ventilators. However, supplies for dialysis treatment, including dialysate, have also run dangerously low in hospitals at the epicenter of the pandemic. Therefore, there is an urgent need to develop materials that can efficiently and rapidly regenerate dialysate, removing toxins and restoring electrolyte concentrations so that this vital resource remains readily available. In this work, Ti3C2Tx, a two-dimensional transition-metal carbide (MXene) that is known to efficiently adsorb urea, was used to remove creatinine and uric acid from an aqueous solution and dialysate, with a maximum adsorption capacity of 45.7 and 17.0 mg/g, respectively. We systematically analyzed and modeled the adsorption kinetics, isotherms, and thermodynamics, thus determining the rate-limiting step and adsorption mechanism. A fixed-bed column loaded with Ti3C2Tx was designed to further evaluate the adsorption performance under continuous fluid-flow conditions, mirroring conditions of continuous renal replacement therapy modalities. The maximum capacity and 50% breakthrough volume were calculated to further approach the practical application of Ti3C2Tx for removal of uremic toxins. Our findings suggest that Ti3C2Tx has the potential to be used as an efficient sorbent for the regeneration of dialysate, allowing for accelerated dialysate regeneration by removing filtered toxins and leading to more portable dialysis devices.

Creatinine/chemistry , Dialysis Solutions/chemistry , Titanium/chemistry , Toxins, Biological/chemistry , Adsorption , Humans , Renal Dialysis/methods , Urine/chemistry
Biochem Pharmacol ; 181: 114096, 2020 11.
Article in English | MEDLINE | ID: covidwho-597939


Venomous animals have evolved toxins that interfere with specific components of their victim's core physiological systems, thereby causing biological dysfunction that aids in prey capture, defense against predators, or other roles such as intraspecific competition. Many animal lineages evolved venom systems independently, highlighting the success of this strategy. Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. We provide examples of each of these areas of venom research, highlighting the potential that venom molecules hold for basic research and drug development.

Biomedical Research/methods , Drug Discovery/methods , Peptides/pharmacology , Toxins, Biological/pharmacology , Venoms/pharmacology , Animals , Drug Development/methods , Humans , Molecular Targeted Therapy/methods , Peptides/chemistry , Peptides/therapeutic use , Protein Conformation , Toxins, Biological/chemistry , Toxins, Biological/therapeutic use , Venoms/chemistry , Venoms/metabolism , Venoms/therapeutic use