Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP’s). MARK4 is known for its major role in tau phosphorylation via phosphorylating Ser262 residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer’s disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson’s disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of −6.9 kcal/mol forming interactions with binding pocket’s critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC50 = 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 106 M−1. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.

Human serum albumin (HSA), an abundant plasma protein, binds to various ligands, acting as a transporter for numerous endogenous and exogenous substances. Galantamine (GAL), an alkaloid, treats cognitive decline in mild to moderate Alzheimer’s disease and other memory impairments. A vital step in pharmacological profiling involves the interaction of plasma protein with the drugs, and this serves as an essential platform for pharmaceutical industry advancements. This study is carried out to understand the binding mechanism of GAL with HSA using computational and experimental approaches. Molecular docking revealed that GAL preferentially occupies Sudlow’s site I, i.e., binds to subdomain IIIA. The results unveiled that GAL binding does not induce any conformational change in HSA and hence does not compromise the functionality of HSA. Molecular dynamics simulation (250 ns) deciphered the stability of the HSA–GAL complex. We performed the fluorescence binding and isothermal titration calorimetry (ITC) to analyze the actual binding of GAL with HSA. The results suggested that GAL binds to HSA with a significant binding affinity. ITC measurements also delineated thermodynamic parameters associated with the binding of GAL to HSA. Altogether, the present study deciphers the binding mechanism of GAL with HSA.

The aim of this study is to measure the magnitude and describe morbidity pattern, management, and outcome of non-traffic unintentional injuries among a pediatric age group at a tertiary hospital in Riyadh, Saudi Arabia. Materials and Methods This is a retrospective descriptive cross-sectional study conducted at Emergency Department (ED) of King Abdul-Aziz Medical City, Riyadh, Saudi Arabia, including all pediatric patients aged 0 to 14 years who had non-traffic unintentional injuries and admitted to the ED from January 1, 2016, to December 31, 2017. The number of children included for the specified period was 491 patients. Results A total of 491 patients were included over the study period; the majority were males (64%). The most common injury types were fractures, dislocations, and subluxations (47.3%) followed by penetration injuries (21%) and burn injuries (17.5%). The most involved body site was the upper limbs (45.2%) followed by head and neck (24.2%) and lower limbs (17.3%). Fall was the leading mechanism of injuries (47.7%) followed by hot liquids and chemical exposure (14.5%). Most of the cases resulted in no significant disabilities (40%), 21.6% resulted in short-term disability, 24.2% had long-term disability, and 12.8% had permanent disabilities. There were six cases (1.2%) of mortality. Conclusions Non-traffic unintentional pediatric injuries are common with significant morbidity and complications, and most of them are preventable. More efforts are needed to increase public awareness and to implement preventive measures at households and public places.