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Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid arthritis.

OBJECTIVE: Over-proliferation of synovium is a key event of invasive pannus formation and cartilage damage in the progression of RA disease. … enzyme A Synthetase Long Chain 4 (ACSL4) and an increase in Ferritin heavy chain 1 (FTH1), GPX4 and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Although both oxidation and antioxidation levels of lipids were higher in RA FLS than in healthy controls, the increase in antioxidation was slightly higher than oxidation. RNA-seq an …

Atorvastatin Induces Mitochondria-Dependent Ferroptosis via the Modulation of Nrf2-xCT/GPx4 Axis.

As one of the cornerstones of clinical cardiovascular disease treatment, statins have an extensive range of applications. However, statins c … ase in nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPx4), and xCT cystine-glutamate antiporter (the main component is SLC7A11) are involved in atorvastatin-induced muscular cell ferroptosis and damage. The downregulation of GPx4 in mitochondria-mediated ferroptosis signaling may be the core of it. In conclusion, our findi …

Инженерные антивирусные агенты через поверхностный плазмонный резонанс.

Резонанс поверхностного плазмона (SPR) используется для измерения гемагглютинина (HA), привязывающегося к димеру циановирина-N (CV-N) и мониторинга взаимодействия между манносилированными пептидами и связующим участком CV-N. Согласно сообщениям, вирусные скачки gp120, HA и Eбола-гликопротеин (GP) 1,2 связывают как участки с высокой, так и участки с низкой долей связывания на димерический CVN2. Диманносилированный пептид HA также связан на двух участках с низкой степенью сцепления с модифицированной молекулой CVN2, которая имеет участок высокой интенсивности для соответствующего лиганда и мутир

Совпадение в аннотации оригинала
Surface plasmon resonance (SPR) is used to measure hemagglutinin (HA) binding to domain-swapped Cyanovirin-N (CV-N) dimer and to monitor int … number of disulfide bridges in domain-swapped CVN2, which are decreased from 4 to 2 by substituting cystines into polar residue pairs of glutamic acid and arginine, results in reduced binding affinity to HA. Among the strongest interactions, Ebola GP1,2 is bound by CVN2 with two high-affinity binding sites in the lower nanomolar range using the envelope g …

Mediation of metal chelation in cysteine-derived tetramate systems.

A study of bicyclic tetramates modified with a bulky ester, which leads to steric hindrance of distal chelating atoms as a route for the alteration of metal binding ability is reported. This approach required the development of a direct method for the synthesis of different esters of cysteine from cystine, which then provided access to bicyclic tetramates by Dieckmann cyclisation. Further derivation to ketones and carboxamides by Grignard addition and transamination reactions respectively provided rapid access to a chemical library of tetramates with diverse substitution. Of interest is that b…

Circulating amino acid signature in older people with Parkinson's disease: A metabolic complement to the EXosomes in PArkiNson Disease (EXPAND) study.

BACKGROUND AND AIM: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in old age. Neurotoxicity of dopaminerg … or participants with PD and 94.7 ± 3.0% for non-PD controls. Higher levels of β-amino butyric acid, cystine, ornithine, phosphoethanolamine, and proline defined the circulating amino acid profile of older people with PD. Controls were characterized by higher concentrations of 3-methyl-histidine, citrulline, and serine. CONCLUSION: Our findings indicate t …

Targeting Glutathione and Cystathionine β-Synthase in Ovarian Cancer Treatment by Selenium-Chrysin Polyurea Dendrimer Nanoformulation.

Ovarian cancer is the main cause of death from gynecological cancer, with its poor prognosis mainly related to late diagnosis and chemoresistance (acquired or intrinsic) to conventional alkylating and reactive oxygen species (ROS)-generating drugs. We and others reported that the availability of cysteine and glutathione (GSH) impacts the mechanisms of resistance to carboplatin in ovarian cancer. Different players in cysteine metabolism can be crucial in chemoresistance, such as the cystine/glutamate antiporter system Xc (xCT) and the H2S-synthesizing enzyme cystathionine β-synthase (CBS) in th…

Klebsiella pneumoniae Expressing VIM-1 Metallo-β-Lactamase Is Resensitized to Cefotaxime via Thiol-Mediated Zinc Chelation.

Antibiotic-resistant Klebsiella pneumoniae isolates constitute a great clinical challenge. One important resistance mechanism in K. pneumoni … rometric thiol assay, and the reducing ability of the supernatant was measured with a fluorescent l-cystine probe. Urine samples from healthy volunteers were used to validate findings ex vivo VIM-1-expressing K. pneumoniae regained susceptibility to CTX when grown in supernatants from HT-29 cells. This effect was mediated via free thiols in the supernatan …

Molecular interactions of the gating modifier toxin ProTx-II with NaV 1.5: implied existence of a novel toxin binding site coupled to activation.

Voltage-gated Na(+) channels are critical components in the generation of action potentials in excitable cells, but despite numerous structure-function studies on these proteins, their gating mechanism remains unclear. Peptide toxins often modify channel gating, thereby providing a great deal of information about these channels. ProTx-II is a 30-amino acid peptide toxin from the venom of the tarantula, Thrixopelma pruriens, that conforms to the inhibitory cystine knot motif and which modifies activation kinetics of Na(v) and Ca(v), but not K(v), channels. ProTx-II inhibits current by shifting …

Insect-selective spider toxins targeting voltage-gated sodium channels.

The voltage-gated sodium (Na(v)) channel is a target for a number of drugs, insecticides and neurotoxins. These bind to at least seven identified neurotoxin binding sites and either block conductance or modulate Na(v) channel gating. A number of peptide neurotoxins from the venoms of araneomorph and mygalomorph spiders have been isolated and characterized and determined to interact with several of these sites. These all conform to an 'inhibitor cystine-knot' motif with structural, but not sequence homology, to a variety of other spider and marine snail toxins. Of these, spider toxins several s…

Dietary determinants of plasma homocysteine concentrations.

Severe hyperhomocysteinemia is typically caused by rare enzymatic defects or by renal failure. In contrast, mild to moderate hyperhomocystei … y, but these changes are transient, and levels return to normal after an overnight fast. Serine and cystine also influence the methionine-induced postprandial rise in tHcy concentrations. In conclusion, alteration in dietary intake or use of folic acid supplements can substantially lower tHcy concentrations. However, it is not known whether lowering tHcy …

Solution structure of two insect-specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel.

Delta-paluIT1 and delta-paluIT2 are toxins purified from the venom of the spider Paracoelotes luctuosus. Similar in sequence to mu-agatoxins … and molecular dynamics. The structures of delta-paluIT1 and delta-paluIT2 belong to the inhibitory cystine knot structural family, i.e. a compact disulfide-bonded core from which four loops emerge. Delta-paluIT1 and delta-paluIT2 contain respectively two- and three-stranded anti-parallel beta-sheets as unique secondary structure. We compare the structure …

Solution structure of Pi4, a short four-disulfide-bridged scorpion toxin specific of potassium channels.

Pi4 is a short toxin found at very low abundance in the venom of Pandinus imperator scorpions. It is a potent blocker of K(+) channels. Like … of peptides obtained by proteolysis of nPi4. Both approaches indicate that the pairing of the half-cystines is (6)C-(27)C, (12)C-(32)C, (16)C-(34)C, and (22)C-(37)C. The structure of the toxin has been determined by using 705 constraints derived from NMR data on sPi4. The structure, which is well defined, shows the characteristic alpha/beta scaffold of s …

Global gene expression analysis in a mouse model for Norrie disease: late involvement of photoreceptor cells.

PURPOSE: Mutations in the NDP gene give rise to a variety of eye diseases, including classic Norrie disease (ND), X-linked exudative vitreoretinopathy (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of prematurity (ROP). The gene product is a cystine-knot-containing extracellular signaling molecule of unknown function. In the current study, gene expression was determined in a mouse model of ND, to unravel disease-associated mechanisms at the molecular level. METHODS: Gene transcription in the eyes of 2-year-old Ndp knockout mice was compared with that in the eyes of a…

Apoptosis induction in lymphoma cells: thiol deprivation versus thiol excess.

We studied the effects of thiol availability on apoptosis induction in B-cell lymphoma 38C13, T-cell lymphoma EL4, and also other cells. Compounds with a free SH group are required for survival and growth of 38C13 cells but not of EL4 cells. Thiol deprivation (2-mercaptoethanol concentrations about 0.3 microM and lower) induced apoptosis in 38C13 cells. On the other hand, thiol excess (2-mercaptoethanol concentrations higher than 300 microM) induced apoptosis in 38C13 cells and EL4 cells as well as in other cells (e.g. Raji, HeLa). L-cystine and non-thiol antioxidant ascorbic acid were unable …

Evaluation of the DipStreak, a new device with an original streaking mechanism for detection, counting, and presumptive identification of urinary tract pathogens.

DipStreak is a new urine culture device with two types of agar attached back-to-back on a plastic paddle. It combines dip-slide technology and an original streaking inoculation mechanism, allowing for bacterial counting and colony isolation. The performance of the DipStreak device with two different medium formulations, CHROMagar and MacConkey media in study A and UriSelect 3 and MacConkey media in study B, was evaluated and compared to that of the reference streak method by using plates of cystine-lactose-electrolyte-deficient (CLED) agar, tryptic soy agar with 5% sheep blood, and UriSelect 3…

Under proper control, oxidation of proteins with known chemical structure provides an accurate and absolute method for the determination of their molar concentration.

Oxidation at 120 degrees C of inorganic and organic (including amino acids, di- and tripeptides) model compounds by K(2)Cr(2)O(7) in the presence of H(2)SO(4) (mass fraction: 0.572), Ag(2)SO(4) (catalyst), and HgSO(4) results in the quantitative conversion of their C-atoms into CO(2) within 24 h or less. Under these stressed, well-defined conditions, the S-atoms present in cysteine and cystine residues are oxidized into SO(3) while, interestingly, the oxidation states of all the other (including the N-) atoms normally present in a protein do remain quite unchanged. When the chemical structure …

Prevention of acetaminophen- and naphthalene-induced cataract and glutathione loss by CySSME.

PURPOSES: To assess the efficacy of 2-mercaptoethanol/L-cysteine mixed disulfide (CySSME) as an L-cysteine prodrug suitable for glutathione biosynthesis in rat lenses in vitro, as an agent for the prevention of acetaminophen- and naphthalene-induced murine cataract in genetically-susceptible mice, and as an agent for maintenance of near-normal glutathione levels in lenses and livers of mice subjected to acetaminophen and naphthalene at cataractogenic doses. METHODS: Synthetic CySSME was added as a prodrug to rat lens culture medium devoid of L-cystine and L-methionine but containing [14C(U)]-…

Interactive effects of neurohypophyseal neuropeptides with receptor antagonists on passive avoidance behavior: mediation by a cerebral neurohypophyseal hormone receptor?

The neurohypophyseal neuropeptides (Arg8)-vasopressin (AVP) and [pGlu4,Cyt6]AVP-(4-8) (where pGlu is pyroglutamic acid and Cyt is cystine) facilitate the retention of one-trial-learning passive avoidance behavior in rats when administered into the cerebral ventricle immediately after the learning trial. The fragment [pGlu4,Cyt6]AVP-(4-8) was considerably more effective than AVP. Oxytocin (OXT) and [pGlu4,Cyt6]OXT-(4-8) have the opposite effect and attenuate passive avoidance behavior also when administered into the cerebral ventricle after the learning trial. Again the fragment was more active…

Electromagnetic extracorporeal shock wave lithotripsy in children.

Extracorporeal shock wave lithotripsy (ESWL) was performed for the treatment of urinary tract calculi in 28 children. All treatments were do … ssions and 11 months of followup in 1, and 7 mm. after 3 sessions and 3 months of followup in 1). A cystine staghorn stone necessitated open nephrolithotomy after 3 sessions without any fragmentation. One impacted sacroiliac ureteral stone required endoscopic laser lithotripsy. Except for these 2 failures no adjuvant procedures were needed. There were no …

Intestinal absorption of glucose and amino acids in chickens administered monensin.

Effects of the ionophoric anticoccidial agent monensin on glucose and amino acid absorption were investigated in young broiler chickens. Chi … ino acid being markedly affected by monensin. Dietary monensin alone had no effect on absorption of cystine, isoleucine, methionine, or threonine. Inclusion of monensin in the saline solution depressed methionine absorption but only when birds also had been fed the diet containing monensin. Monensin in the saline solution depressed isoleucine absorption i …