Notes

Your MttB superfamily fellow member MtyB through the human stomach symbiont Eubacterium limosum is really a cobalamin-dependent γ-butyrobetaine methyltransferase.
BACKGROUND Magnesium is an essential element related with biochemistry of the brain and different types of depression have been associated with its deficiency. METHODS The structure of a novel magnesium bis(DL-pyroglutamate) (Mg(DL-pGlu)2) was elucidated by X-ray crystallography. Wistar rats were used in the in vivo experiments. The antidepressant-Iike effect was assessed by the forced swim test (FST) and the antinociceptive activity was evaluated using hot plate test. In both, non-specific effects were evaluated by the open field test. Anti-thyroid activity was examined using Lang's method. Albumin binding behavior was evaluated by 3D fluorescence spectroscopy. RESULTS For the Mg(DL-pGlu)2 complex (30 mg/kg), the FST test on Wistar rats revealed a decrease of 22% in the immobility time and an increment of 106% in the swimming time. The compound alters neither the locomotor activity nor the body weight after chronic administration. At the same dose, it showed antinociceptive activity, increasing the response latency. It blocks iodination reactions generating a charge transfer complex with iodine hence indicating anti-thyroid activity (Kc = 45366.5 ±29 M 1). Albumin 3D fluorescence spectroscopy experiments showed intensity increase of peak A and decrease of peak B. CONCLUSIONS The results showed that the new compound produced a lowering of the immobility time and an increment of the swimming ability of the rats. The compound is able to increase the response latency in 70.0%, to capture iodine (anti-thyroid activity) and to interact with albumin through covalent type of interaction of the free NH groups.BACKGROUND Sepsis initiates an inflammatory response that causes widespread injury, and candidates for related myocardial depressant factors include cytokines and nitric oxide (NO). Nuclear factor kappa-B (NF-KB) stimulated by toll-like receptor 4 activation in sepsis mediates the transcription of multiple proinflammatory genes. These inflammatory mediators can cause myocardial dysfunction, which may deteriorate sepsis outcomes. To address this risk, we investigated the potential beneficial effects of a novel isoquinolines derivative, CYY054c, in LPS-induced inflammatory response leading to endotoxemia. METHODS The effects of CYY054c on cytokine and inflammatory-related protein production were evaluated in lipopolysaccharide (LPS)-stimulated macrophages. To determine whether CYY054c alleviates inflammatory storm-induced myocardial dysfunction in vivo, LPS was injected in rats, and cardiac function was measured by a pressure-volume loop. RESULTS CYY054c inhibited LPS-induced NF-KB expression in macrophages and reduced the release of tumor necrosis factor-alpha (TNF-1α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In the animal studies, CYY054c alleviated LPS-upregulated plasma TNF-ct, IL-1β, IL-6, and NO concentrations, as well as cardiac monocyte chemotactic protein-1, iNOS, and COX-2 expression in rats, contributing to the improvement of cardiac function during endotoxemia. CONCLUSIONS The reduction of NF-KB-mediated inflammatory mediators and the maintenance of hemodynamic performance by CYY054c improved the outcomes during endotoxemia. CYY054c may be a potential therapeutic agent for sepsis.BACKGROUND Methylphenidate (Ritalin®) is a psychostimulant used chronically to treat attention deficit hyperactivity disorder. Methylphenidate acts by preventing the reuptake of dopamine and norepinephrine, resulting in an increase in these neurotransmitters in the synaptic cleft. Excess dopamine can be autoxidized to a quinone that may lead to oxidative stress. The antioxidant, glutathione helps to protect the cell against quinones via conjugation reactions; however, depletion of glutathione may result from excess quinone formation. Chronic exposure to methylphenidate appears to sensitize dopaminergic neurons to the Parkinsonian toxin l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). We hypothesized that oxidative stress caused by the autooxidation of the excess dopamine renders dopaminergic neurons within the nigrostriatal pathway to be more sensitive to MPTP. Neuronal Signaling agonist METHODS To test this hypothesis, male mice received chronic low or high doses of MPH and were exposed to saline or MPTP following a 1-week washout. Quinone formation in the striatum was examined via dot blot, and striatal GSH was quantified using a glutathione assay. RESULTS Indeed, quinone formation increased with increasing doses of methylphenidate. Additionally, methylphenidate dose-dependently resulted in a depletion of glutathione, which was further depleted following MPTP treatment. CONCLUSIONS Thus, the increased sensitivity of dopamine neurons to MPTP toxicity following chronic methylphenidate exposure may be due to quinone production and subsequent depletion of glutathione.BACKGROUND The significance of the free radicals is emphasized in the pathophysiology of diabetes and the progression of chronic diabetic complications. Smoking cigarettes increases the risk of developing type II diabetes and intensifies pathophysiological processes during the development of type I diabetes. Tobacco smoke is also additional source of free radicals. Moreover, smoking causes variety of adverse effects on organs, that have no direct contact with the tobacco smoke itself. The objective of the study was to examine the effects of tobacco smoke on the serum concentrations of relevant oxidative stress markers such as total protein (TP), reduced glutathione (GSH), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS), as well as renal (creatinine, urea) and liver function (alkaline phosphatase, ALP; alanine aminotransferase, ALT; aspartate aminotransferase, AST) among animals with induced diabetes after administration of a single dose of streptozotocin (65 mg/kg, ip). METHODS The markers of oxidative stress and biochemical parameters were determined using spectrophotometric methods. As a biomarker of exposure to tobacco smoke, cotinine was determined using high-performance liquid chromatography with diode array detection (HPLC-DAD). RESULTS Tobacco smoke exposure of diabetic rats was manifested by significantly elevated liver enzymes activity - ALT (p less then 0.05) and ALP (p less then 0.01), higher creatinine and urea concentration (p less then 0.01), lower GSH amount (p less then 0.05), and higher GST activity (p less then 0.05). CONCLUSIONS Tobacco smoking induce liver and renal damage through the mechanisms including increased oxidative stress.
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