SURF1 Deficiency: Expanding on Disease Phenotype and Assessing Disease Burden by Describing Clinical and Biochemical Phenotype.

Leigh syndrome, a severe neurological disorder is commonly caused by homozygous or bi-allelic pathogenic variants in the SURF1 gene. SURF1 deficiency leads to dysfunction of Cytochrome C Oxidase (COX) activity, which is crucial for mitochondrial oxidative phosphorylation. Understanding COX activity's correlation with disease severity is essential for developing SURF1 Leigh Syndrome biomarkers.

AAV-based in vivo gene therapy for neurological disorders.

Recent advancements in gene supplementation therapy are expanding the options for the treatment of neurological disorders. Among the available delivery vehicles, adeno-associated virus (AAV) is often the favoured vector. However, the results have been variable, with some trials dramatically altering the course of disease whereas others have shown negligible efficacy or even unforeseen toxicity.

A novel single-chain enzyme complex with chain reaction properties rapidly producing thromboxane A and exhibiting powerful anti-bleeding functions.

Uncontrollable bleeding is still a worldwide killer. In this study, we aimed to investigate a novel approach to exhibit effective haemostatic properties, which could possibly save lives in various bleeding emergencies. According to the structure-based enzymatic design, we have engineered a novel single-chain hybrid enzyme complex (SCHEC), COX-1-10aa-TXAS.

Proteomic analysis of male rat nucleus accumbens, dorsal hippocampus and amygdala on conditioned place aversion induced by morphine withdrawal.

Addiction is characterized by compulsive drug seeking and taking behavior, which is thought to result from persistent neuroadaptations, encoded by changes of gene expression. We previously demonstrated that the changes in synaptic plasticity were required for the formation of aversive memories associated with morphine withdrawal. However, the proteins involved in synaptic plasticity and aversive memory formation have not been well explored.

Creating a mouse model resistant to induced ischemic stroke and cardiovascular damage.

Vascular prostanoids, isomerized from an intermediate prostaglandin (PG), H, produced by cyclooxygenase (COX), exert various effects on the vascular system, both protective and destructive. During endothelial dysfunction, vascular protector prostacyclin/prostaglandin I (PGI) is decreased, while inflammatory PGE and thrombotic TXA are increased. Therefore, our research aim was to reverse the event by controlling PGH metabolism by generating an in vivo model via enzymatic engineering of COX-1 and prostacyclin synthase (PGIS).

Accurate quantification of PGE in the polyposis in rat colon (Pirc) model by surrogate analyte-based UPLC-MS/MS.

An accurate and reliable UPLC-MS/MS method is reported for the quantification of endogenous Prostaglandin E2 (PGE) in rat colonic mucosa and polyps. This method adopted the "surrogate analyte plus authentic bio-matrix" approach, using two different stable isotopic labeled analogs - PGE-d9 as the surrogate analyte and PGE-d4 as the internal standard. A quantitative standard curve was constructed with the surrogate analyte in colonic mucosa homogenate, and the method was successfully validated with the authentic bio-matrix.

The key residue within the second extracellular loop of human EP3 involved in selectively turning down PGE- and retaining PGE-mediated signaling in live cells.

Key residues and binding mechanisms of PGE and PGE on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE and PGE docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site.

Down-regulation of dorsal striatal RhoA activity and impairment of working memory in middle-aged rats.

The effect of aging on learning and memory has been intensively studied. However, the mechanisms underlying impairment of memory functions at middle age remains inexplicit. To address this question, we assessed the spatial working memory and long-term memory of middle-aged (16-18 months) rats with delayed alternation in T-maze and water maze task respectively.