Exploring the Utility of ssDNA Aptamers Directed against Snake Venom Toxins as New Therapeutics for Snakebite Envenoming

Snakebite is a neglected tropical disease that causes considerable death and disability in the tropical world. Although snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Antivenoms are the mainstay therapy for treating the toxic effects of snakebite, but despite saving thousands of lives annually, these therapies are associated with limited cross-snake species efficacy due to venom variation, which ultimately restricts their therapeutic utility to particular geographical regions. In this study, we sought to explore the potential of ssDNA aptamers as toxin-specific inhibitory alternatives to antibodies. As a proof of principle model, we selected snake venom serine protease toxins, which are responsible for contributing to venom-induced coagulopathy following snakebite envenoming, as our target. Using SELEX technology, we selected ssDNA aptamers against recombinantly expressed versions of the fibrinogenolytic SVSPs ancrod from the venom of C. rhodostoma and batroxobin from B. atrox. From the resulting pool of specific ssDNA aptamers directed against each target, we identified candidates that exhibited low nanomolar binding affinities to their targets. Downstream aptamer-linked immobilised sorbent assay, fibrinogenolysis, and coagulation profiling experiments demonstrated that the candidate aptamers were able to recognise native and recombinant SVSP toxins and inhibit the toxin- and venom-induced prolongation of plasma clotting times and the consumption of fibrinogen, with inhibitory potencies highly comparable to commercial polyvalent antivenoms. Our findings demonstrate that rationally selected toxin-specific aptamers can exhibit broad in vitro cross-reactivity against toxin isoforms found in different snake venoms and are capable of inhibiting toxins in pathologically relevant in vitro and ex vivo models of venom activity. These data highlight the potential utility of ssDNA aptamers as novel toxin-inhibiting therapeutics of value for tackling snakebite envenoming.     

Effects of sleep intervention on glucose control: A narrative review of clinical evidence

BackgroundOptimizing sleep has been recently gained exposure as a promising lifestyle consideration to aid in the control of diabetes. The evidence to support the impact of sleep quantity and quality on blood glucose control is largely acknowledged. This study aimed to review all published randomized controlled trials (RCTs) investigating the relationship between sleep and glucose control to synthesize an accurate overview.MethodLiterature from PubMed and Google Scholar was searched using the listed search terms to obtain RCTs on the role of sleep in glucose homeostasis. Seven RCTs were eligible and included in our review. References in these RCTs were screened for the presentation of the pathophysiology of metabolic disturbances relating to the sleep duration, and the relevant factors affecting blood glucose concentration.ResultsSleep deprivation and poor sleep quality are connected with blood glucose disturbance and reduction of insulin sensitivity. This leaves diabetic patients at an increased risk of glucose level fluctuations. However, the function of β-cells was likely to be conserved after 14-days of sleep deprivation. Sleep extension from 7 to 14 days improved blood glucose control and insulin sensitivity in both healthy and diabetes participants. Diabetes sleep education and personalized interventions that reduced stress and improved sleep quality contributed to glucose homeostasis in diabetic patients. Overall improving one’s sleep hygiene was found to improve glucose control in diabetic patients.ConclusionLonger or short-term sleep deprivation may negatively affect glucose homeostasis, although the body temporarily compensates for the impaired function of β-cells when reduced sleep lasted up to 14 days. Thus, we recommend optimum sleep duration and optimistic sleep duration and sleep quality for decreasing risk and progression of diabetes.     

Double-blind trial of recombinant γ-interferon versus placebo in the treatment of rheumatoid arthritis

One hundred five patients were enrolled in a 12-week, randomized, prospective, double-blind, placebo-controlled trial of recombinant human γ-interferon (rHuγ-IFN) for the treatment of rheumatoid arthritis. Fifty-four patients received rHuγ-IFN and 51 received placebo. Forty-two patients in each group completed the 12-week trial. Some clinical improvement occurred in both groups of patients. Although the improvement with rHuγ-IFN was greater than that with placebo, the differences were generally not statistically significant.