NMR and encephalopathy

Urease is an amidohydrolase enzyme that is responsible for fatal morbidities in the human body, such as catheter encrustation, encephalopathy, peptic ulcers, hepatic coma, kidney stone formation, and many others. In recent years, scientists have devoted considerable efforts to the quest for efficient urease inhibitors. In the pharmaceutical chemistry, the thiourea skeleton plays a vital role. Thus, the present work focused on the development and discovery of novel urease inhibitors and reported the synthesis of a set of 1-aroyl-3-[3-chloro-2-methylphenyl] thiourea hybrids with aliphatic and aromatic side chains 4a - j ...

Amyloid aggregates of specific proteins constitute important pathological hallmarks in many neurodegenerative diseases, defining neuronal degeneration and disease onset. Recently, increasing numbers of patients show comorbidities and overlaps between multiple neurodegenerative diseases, presenting distinct phenotypes. Such overlaps are often accompanied by colocalizations of more than one amyloid protein, prompting the question of whether direct interactions between different amyloid proteins could generate heterotypic amyloids...

In the present work we reported the synthesis of Schiff bases from 4-phenoxy-5-sulfamoylbenzoic acid motif. The reaction was carried out by substitution of different aldehyde and ketones at sulfamoyl group of sulfamoylbenzoic acid. The generated substituted products (4a-4i) possessed potent structure activity relationship and exhibited drug like properties. The structures of synthesized compounds were characterized on the basis of FT-IR, 1H NMR, 13C NMR and mass spectroscopic data. The effects of synthesized products were investigated on urease enzyme through anti-urease enzyme inhibition assay (Weather burn method)...

Diabetes mellitus can result in severe complications, such as neurodegenerative diseases including cognitive impairment and dementia. The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, is a novel antidiabetic drug with neuroprotective effects against neurodegenerative diseases. In this study, we explored the protective effect of liraglutide on SH-SY5Y cells exposed to methylglyoxal (MG), a byproduct of glucose metabolism that plays a key role in the development of diabetic encephalopathy. We found that liraglutide reduced the MG-induced oxidative stress, increased the activity of superoxide dismutase (SOD) and expression levels of P22phox, Gp91phox, and Xdh genes, and reduced reactive oxygen species (ROS) content...

To investigate the metabolic changes in type C hepatic encephalopathy (CHE) rats after reducing manganese (Mn) intake. A total of 80 Sprague-Dawley rats were divided into control group and CHE groups (induced by intraperitoneal injection of thioacetamide at a dose of 250 mg/kg of body weight twice a week for 6 weeks). CHE rats were subdivided into 1Mn group (fed a standard diet, with 10 mg Mn/kg feed), 0.5Mn group (half-Mn diet), 0.25Mn group (quarter-Mn diet) and 0Mn group (no-Mn diet) for 4 to 8 weeks...

Diabetes seriously endangers public health and brings a heavy economic burden to the country. Inflammation is one of the main inducing factors of type-2 diabetes (T2D) and may cause some complications of diabetes, such as diabetic encephalopathy and peripheral neuropathy. In-depth research and development of drugs to cure diabetes and complications are of great significance. Pueraria lobate is a medicinal herb used in several countries to treat many diseases. Here, two new polysaccharides (PLB-1-1 and PLB-1-2) were isolated and purified from the root of Pueraria lobata with molecular weights of 9...

Urease has become an important therapeutic target because it stimulates the pathogenesis of many human health conditions, such as pyelonephritis, the development of urolithiasis, hepatic encephalopathy, peptic ulcers, gastritis and gastric cancer. A series of alkyl chain-linked thiourea derivatives were synthesized to screen for urease inhibition activity. Structure elucidation of these compounds was done by spectral studies, such as IR, 1 H NMR and 13 C NMR, and MS analysis. In vitro urease enzyme inhibition assay revealed that compound 3c was the most potent thiourea derivative among the series with IC50 values of 10...

Fetal, perinatal, and neonatal asphyxia are vital health issues for the most vulnerable groups in human beings, including fetuses, newborns, and infants. Severe reduction in oxygen and blood supply to the fetal brain can cause hypoxic-ischemic encephalopathy (HIE), leading to long-term neurological disorders, including mental impairment and cerebral palsy. Such neurological disorders are major healthcare concerns. Therefore, there has been a continuous effort to develop clinically useful diagnostic tools for accurately and quantitatively measuring and monitoring blood and oxygen supply to the fetal and neonatal brain to avoid severe consequences of asphyxia HIE and neonatal encephalopathy...

The cellular prion protein (PrPC ) is a mainly α-helical 208-residue protein located in the pre- and postsynaptic membranes. For unknown reasons, PrPC can undergo a structural transition into a toxic, β-sheet rich scrapie isoform (PrPSc ) that is responsible for transmissible spongiform encephalopathies (TSEs). Metal ions seem to play an important role in the structural conversion. PrPC binds Zn(II) ions and may be involved in metal ion transport and zinc homeostasis. Here, we use multiple biophysical techniques including optical and NMR spectroscopy, molecular dynamics simulations, and small angle X-ray scattering to characterize interactions between human PrPC and Zn(II) ions...

Objective: To investigate the effect of electroacupuncture (EA) on cognitive dysfunction in rats with hepatic encephalopathy and its underlying mechanism. Methods: Fifty Wistar rats were randomly divided into a normal group ( n  = 10) and model group ( n  = 40). Rat models of hepatic encephalopathy were established by administration of carbon tetrachloride and thioacetamide for a total of 12 weeks. At the 9th week after modeling, rats with cognitive impairment in the model group were identified by conducting the Morris water maze test, which were then randomly divided into a control group (CCl4 ) and treatment groups including EA group (CCl4  + EA), lactulose group (CCl4  + Lac), and EA plus lactulose group (CCl4  + CM), with 9 rats in each group...

Urease plays a significant role in the pathogenesis of urolithiasis pyelonephritis, urinary catheter encrustation, hepatic coma, hepatic encephalopathy, and peptic acid duodenal ulcers. Salvinia molesta was explored to identify new bioactive compounds with particular emphasis on urease inhibitors. The aqueous methanol extract was fractionated using solvents of increasing polarity. A series of column chromatography and later HPLC were performed on butanol extract. The structures of the resulting pure compounds were resolved using NMR (1D and 2D), infrared, and mass spectroscopy...

Human prion disease, also known as transmissible spongiform encephalopathy (TSEs), is caused by the conformational conversion of the normal cellular prion protein (PrPC ) into the scrapie form (PrPSc ). Pathogenic point mutations of prion proteins typically facilitate conformational conversion and lead to inherited prion diseases. A previous study has demonstrated that the pathogenic G131V mutation of human prion protein (HuPrP) brings in Gerstmann-Sträussler-Scheinker syndrome. However, the three-dimensional structure and dynamic features of the HuPrP(G131V) mutant remain unclear...

The WDR45 gene is localized on the X-chromosome and variants in this gene are linked to six different neurodegenerative disorders, i.e., ß-propeller protein associated neurodegeneration, Rett-like syndrome, intellectual disability, and epileptic encephalopathies including developmental and epileptic encephalopathy, early-onset epileptic encephalopathy and West syndrome and potentially also specific malignancies. WDR45/WIPI4 is a WD-repeat β-propeller protein that belongs to the WIPI (WD repeat domain, phosphoinositide interacting) family...

BACKGROUND: ALG13-CDG belongs to the congenital disorders of glycosylation (CDG), which is an expanding group of multisystemic metabolic disorders caused by the N-linked, O-linked oligosaccharides, shared substrates, glycophosphatidylinositol (GPI) anchors, and dolichols pathways with high genetic heterogeneity. Thus, as far as clinical presentation, laboratory findings, and treatment are concerned, many questions are to be answered. Three individuals presented here may serve as a good example of clinical heterogeneity...

The misfolding and aggregation of the human prion protein (PrP) is associated with transmissible spongiform encephalopathies (TSEs). Intermediate conformations forming during the conversion of the cellular form of PrP into its pathological scrapie conformation are key drivers of the misfolding process. Here, we analyzed the properties of the C-terminal domain of the human PrP (huPrP) and its T183A variant, which is associated with familial forms of TSEs. We show that the mutation significantly enhances the aggregation propensity of huPrP, such as to uniquely induce amyloid formation under physiological conditions by the sole C-terminal domain of the protein...

This study aimed to identify hospital neonatal mortality rate (NMR) and the causes of neonatal deaths, and to understand risk factors associated with neonatal mortality in a national tertiary hospital in Cambodia. The study included all newborn infants, aged 0-28 days old, hospitalized in the Pediatrics department of Khmer-Soviet Friendship Hospital between January 2016 and December 2017. In total, 925 infants were included in the study. The mean gestational age was 35.9 weeks (range, 24-42 weeks). Preterm infants and low birth weight accounted for 47...

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders associated with the misfolding and aggregation of the human prion protein (huPrP). Despite efforts into investigating the process of huPrP aggregation, the mechanisms triggering its misfolding remain elusive. A number of TSE-associated mutations of huPrP have been identified, but their role at the onset and progression of prion diseases is unclear. Here we report the NMR assignments of the C-terminal globular domain of the wild type huPrP and the pathological mutant T183A...

Diagnosis and management of patients with septic shock is still a significant challenge for clinicians with its high mortality amongst hospitalized patients. Septic shock is a heterogeneous condition and is usually accompanied by various underlying disease conditions. Dissecting the specific metabolic changes induced by these underlying disease conditions through metabolomics has shown the potential to improve our understanding of the disease's relevant pathophysiological mechanisms, leading to improved treatment...

Catalpol has gained increasing attention for its potential contributions in controlling glycolipid metabolism and diabetic complications, which makes used as a very promising scaffold for seeking new anti-diabetic drug candidates. Acylation derivatives of catalpol crotonate (CCs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surfex-Docking method. Catalpol hexacrotonate (CC-6) was synthesized using microwave assisted method and characterized by FT-IR, NMR, HPLC and HRMS...

Urease enzyme is responsible to catalyze the hydrolysis of urea into carbamate and ammonia. Then carbamate hydrolyzed to ammonia and carbon dioxide. Excess release of ammonia leads to increase pH in stomach that actually encourages the survival of Helicobacter pylori. H. pylori involves in various disorders most commonly peptic ulcer, pyelonephritis, hepatic coma, kidney stone formation, urolithiasis, and encephalopathy. Apart from many pharmacological properties, coumarin and Schiff bases are known to possess urease inhibitory activity...