Development and molecular modeling studies of new thiadiazole piperazine urea derivatives as potential fatty acid amide hydrolase inhibitors.

A series of novel piperazine urea derivatives with thiadiazole moieties were designed, synthesized, and investigated for their inhibition potential against human fatty acid amide hydrolase (hFAAH). The urea derivatives possessing p-chlorophenylthiadiazole and benzylpiperazine fragments (19-22) were effective inhibitors of hFAAH. Notably, compounds with 4-chlorobenzyl (19) and 4-fluorobenzyl (20) tails at the piperazine side were identified as the most active inhibitors with IC50 values of 0.13 and 0.22 µM, respectively. The preincubation test of 19 was in agreement with the irreversible binding mechanism. Molecular docking was performed to explore the potential binding interactions with key amino acid residues at the FAAH active site. These newly identified inhibitors could serve as leads for the further development of potent and selective FAAH inhibitors for FAAH-associated diseases.

Idiopathic acute massive pulmonary embolism in childhood.

Acute pulmonary embolism (PE) is an uncommon clinical condition in childhood. We hereby present a case report of a 10-year-old child who presented to the emergency department with an acute massive PE. He was transferred by ambulance to our emergency department for dyspnea and perioral cyanosis. His parents denied any previous history of illness or familial disease. Arterial blood gas analysis, electrocardiography, and clinical symptoms and signs collectively raised a suspicion of a probable PE. A contrast-enhanced pulmonary computed tomography scan revealed a massive thrombus in the distal part of the right pulmonary artery with no contrast passage into upper, middle, and lower lobar arteries. Upon ascertaining, the diagnosis of PE, intravenous saline infusion, 3 L/min oxygen through nasal route, and subcutaneous enoxaparin 0.4 cc was administered promptly. As our hospital lacked a pediatric intensive care unit and a further need for administration of pharmacological thrombolysis was anticipated, we transferred the patient to a tertiary care center. PE should always be kept in mind as a differential diagnosis in emergency departments even in pediatric patients.

Fabrication of Amyloid Curli Fibers-Alginate Nanocomposite Hydrogels with Enhanced Stiffness.

Alginate hydrogels are biocompatible, biodegradable, low-cost, and widely used as bioinks, cell encapsulates, three-dimensional culture matrices, drug delivery systems, and scaffolds for tissue engineering. Nevertheless, their limited stiffness hinders their use for certain biomedical applications. Many research groups have tried to address this problem by reinforcing alginate hydrogels with graphene, carbon nanotubes, or silver nanoparticles. However, these materials present nanotoxicity issues, limiting their use for biomedical applications. Other studies show that electrospinning or wet spinning can be used to fabricate biocompatible, micro- and nanofibers to reinforce hydrogels. As a relatively simple and cheap alternative, in this study we used bioengineered bacteria to fabricate amyloid curli fibers to enhance the stiffness of alginate hydrogels. We have fabricated for the first time bioengineered amyloid curli fibers-hydrogel composites and characterized them by a combination of (i) atomic force microscopy (AFM) to measure the Young's modulus of the bioengineered amyloid curli fibers and study their topography, (ii) nanoindentation to measure the Young's modulus of the amyloid curli fibers-alginate nanocomposite hydrogels, and (iii) Fourier-transform infrared spectroscopy (FTIR) to analyze their composition. The fabricated nanocomposites resulted in a highly improved Young's modulus (up to 4-fold) and showed very similar physical and chemical properties, opening the window for their use in applications where the properties alginate hydrogels are convenient but do not match the stiffness needed.

Addressable self-immobilization of lactate dehydrogenase across multiple length scales.

Successful nanobiotechnology implementation largely depends on control over the interfaces between inorganic materials and biological molecules. Controlling the orientations of biomolecules and their spatial arrangements on the surface may transform many technologies including sensors, to energy. Here, we demonstrate the self-organization of L-lactate dehydrogenase (LDH), which exhibits enhanced enzymatic activity and stability on a variety of gold surfaces ranging from nanoparticles to electrodes, by incorporating a gold-binding peptide tag (AuBP2) as the fusion partner for Bacillus stearothermophilus LDH (bsLDH). Binding kinetics and enzymatic assays verified orientation control of the enzyme on the gold surface through the genetically incorporated peptide tag. Finally, redox catalysis efficiency of the immobilized enzyme was detected using cyclic voltammetry analysis in enzyme-based biosensors for lactate detection as well as in biofuel cell energy systems as the anodic counterpart. Our results demonstrate that the LDH enzyme can be self-immobilized onto different gold substrates using the short peptide tag under a biologically friendly environment. Depending on the desired inorganic surface, the proposed peptide-mediated path could be extended to any surface to achieve single-step oriented enzyme immobilization for a wide range of applications.

Trimethylaminuria (fish malodour syndrome) in chronic renal failure.

Trimethylaminuria (fish malodour syndrome) is a rare genetic metabolic disorder presented with a body odour which smells like a decaying fish. This odour is highly objectionable, that can be destructive for the social, and work life of the patient. Trimethylamine is derived from the intestinal bacterial degradation of foods that are rich of choline and carnitine. Trimethylamine is normally oxidised by the liver to odourless trimethylamine N-oxide which is excreted in the urine, so, uremia may worsen the condition. Uremia itself may cause more or less unpleasant odour. Poor uremic control may worsen the odour. We reported this case because Trimethylaminuria is not usually considered in the differential diagnosis of malodour in chronic renal failure and it is the first case that shown the association with Trimethylaminuria and chronic renal failure in the literature.