Inflammation, the kynurenines, and mucosal injury during human experimental enterotoxigenic Escherichia coli infection
AbstractEnterotoxigenicEscherichia coli (ETEC) is an important cause of diarrhea in children and travelers, especially in low- and middle-income countries. ETEC is a non-invasive gut pathogen colonizing the small intestinal wall before secreting diarrhea-inducing enterotoxins. We sought to investigate the impact of ETEC infection on local and systemic host defenses by examining plasma markers of inflammation and mucosal injury as well as kynurenine pathway metabolites. Plasma samples from 21 volunteers experimentally infected with ETEC were collected before and 1, 2, 3, and 7  days after ingesting the ETEC dose, and group...
Source: Medical Microbiology and Immunology - March 2, 2024 Category: Microbiology Source Type: research

Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study
CONCLUSION: Biomarkers and metabolites of systemic inflammation, including biomarkers of cellular immune activation, indexes of vitamin B6 homeostasis, and several neuroactive metabolites of the KP pathway, were associated with PSCI.TRIAL REGISTRATION: ClinicalTrials.gov: NCT02650531.PMID:38428649 | DOI:10.1016/j.bbi.2024.02.030 (Source: Brain, Behavior, and Immunity)
Source: Brain, Behavior, and Immunity - March 1, 2024 Category: Neurology Authors: Heidi Vihovde Sandvig Stina Aam Katinka N Alme Stian Lydersen Per Magne Ueland Arve Ulvik Torgeir Wethal Ingvild Saltvedt Anne-Brita Knapskog Source Type: research

Association of Increased Homocysteine Levels with Impaired Folate Metabolism and Vitamin  B Deficiency in Early-Onset Multiple Sclerosis
AbstractThe contents of homocysteine (HCy), cyanocobalamin (vitamin  B12), folic acid (vitamin B9), and pyridoxine (vitamin B6) were analyzed and the genotypes of the main gene polymorphisms associated with folate metabolism (C677T and A1298C of theMTHFR gene, A2756G of theMTR gene and A66G of theMTRR gene) were determined in children at the onset of multiple sclerosis (MS) (with disease duration of no more than six months), healthy children under 18 years (control group), healthy adults without neurological pathology, adult patients with MS at the onset of disease, and adult patients with long-term MS. A significant incr...
Source: Biochemistry (Moscow) - March 1, 2024 Category: Biochemistry Source Type: research

Structure and function of the pyridoxal 5'-phosphate-dependent (PLP) threonine deaminase IlvA1 from Pseudomonas aeruginosa PAO1
Biochem Biophys Res Commun. 2024 Feb 22;704:149710. doi: 10.1016/j.bbrc.2024.149710. Online ahead of print.ABSTRACTIlvA1, a pyridoxal phosphate-dependent (PLP) enzyme, catalyzes the deamination of l-threonine and l-serine to yield 2-ketobutyric acid or pyruvate. To gain insights into the function of IlvA1, we determined its crystal structure from Pseudomonas aeruginosa to 2.3 Å. Density for a 2-ketobutyric acid product was identified in the active site and a putative allosteric site. Activity and substrate binding assays confirmed that IlvA1 utilizes l-threonine, l-serine, and L-allo-threonine as substrates. The enzymatic...
Source: Biochemical and Biophysical Research communications - February 28, 2024 Category: Biochemistry Authors: Haizhu Jia Yujing Chen Yuan Chen Ruihua Liu Qionglin Zhang Mark Bartlam Source Type: research

Structure and function of the pyridoxal 5'-phosphate-dependent (PLP) threonine deaminase IlvA1 from Pseudomonas aeruginosa PAO1
Biochem Biophys Res Commun. 2024 Feb 22;704:149710. doi: 10.1016/j.bbrc.2024.149710. Online ahead of print.ABSTRACTIlvA1, a pyridoxal phosphate-dependent (PLP) enzyme, catalyzes the deamination of l-threonine and l-serine to yield 2-ketobutyric acid or pyruvate. To gain insights into the function of IlvA1, we determined its crystal structure from Pseudomonas aeruginosa to 2.3 Å. Density for a 2-ketobutyric acid product was identified in the active site and a putative allosteric site. Activity and substrate binding assays confirmed that IlvA1 utilizes l-threonine, l-serine, and L-allo-threonine as substrates. The enzymatic...
Source: Biochemical and Biophysical Research communications - February 28, 2024 Category: Biochemistry Authors: Haizhu Jia Yujing Chen Yuan Chen Ruihua Liu Qionglin Zhang Mark Bartlam Source Type: research

Insights into the pathogenesis of primary hyperoxaluria type I from the structural dynamics of alanine:glyoxylate aminotransferase variants
Mutations in alanine:glyoxylate aminotransferase (AGT) leading to protein misfolding cause primary hyperoxaluria type I (PH1). Here, we use hydrogen-deuterium exchange to characterize the structural dynamics of AGT variants. These dynamics are heterogeneously distributed across the structure and different functional sites. Disease-associated variants show local destabilization. Our work provides novel insight into the pathogenic mechanisms causing PH1. Primary hyperoxaluria type I (PH1) is caused by deficient alanine:glyoxylate aminotransferase (AGT) activity. PH1-causing mutations in AGT lead to protein mistargeting and a...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Pavla Vankova, Juan Luis Pacheco ‐Garcia, Dmitry S. Loginov, Atanasio Gómez‐Mulas, Alan Kádek, José Manuel Martín‐Garcia, Eduardo Salido, Petr Man, Angel L. Pey Tags: Research Article Source Type: research

Mexidol, Cytoflavin, and succinic acid derivatives as antihypoxic, anti ‐ischemic metabolic modulators, and ergogenic aids in athletes and consideration of their potential as performance enhancing drugs
The lines between performance enhancement and therapeutic drugs have narrowed in modern times, and it is more difficult than ever to determine when substance crosses the line and is doping agents. Succinate-based drugs as Mexidol and Cytoflavin are antihypoxic, anti-ischemic aids – have similar biological effects as prohibited by WADA metabolic modulators, meldonium and trimetazidine. The role of Mexidol, Cytoflavin as antihypoxant agents is associated with impact on the Krebs cycle, oxidative phosphorylation and ATP production, expression of hypoxia-inducible factor (HIF) . AbstractEmoxypine (ethylmethylhydroxypyridine)...
Source: Drug Testing and Analysis - February 26, 2024 Category: Drugs & Pharmacology Authors: Karol J ędrejko, Oliver Catlin, Timothy Stewart, Bożena Muszyńska Tags: REVIEW ARTICLE Source Type: research

Pyridoxal kinase gene deletion leads to impaired growth, deranged redox metabolism and cell cycle arrest in Leishmania donovani
Biochimie. 2024 Feb 23:S0300-9084(24)00047-6. doi: 10.1016/j.biochi.2024.02.009. Online ahead of print.ABSTRACTPyridoxal kinase (PdxK) is a vitamin B6 salvage pathway enzyme which produces pyridoxal phosphate. We have investigated the impact of PdxK deletion in Leishmania donovani on parasite survivability, infectivity and cellular metabolism. LdPdxK mutants were generated by gene replacement strategy. All mutants showed significant reduction in growth in comparison to wild type. For PdxK mediated biochemical perturbations, only heterozygous mutants and complementation mutants were used as the growth of null mutants were c...
Source: Biochimie - February 25, 2024 Category: Biochemistry Authors: Pradyot Kumar Roy Anindita Paul Sandra Lalchhuanawmi Neerupudi Kishore Babu Sushma Singh Source Type: research

Pyridoxal kinase gene deletion leads to impaired growth, deranged redox metabolism and cell cycle arrest in Leishmania donovani
Biochimie. 2024 Feb 23:S0300-9084(24)00047-6. doi: 10.1016/j.biochi.2024.02.009. Online ahead of print.ABSTRACTPyridoxal kinase (PdxK) is a vitamin B6 salvage pathway enzyme which produces pyridoxal phosphate. We have investigated the impact of PdxK deletion in Leishmania donovani on parasite survivability, infectivity and cellular metabolism. LdPdxK mutants were generated by gene replacement strategy. All mutants showed significant reduction in growth in comparison to wild type. For PdxK mediated biochemical perturbations, only heterozygous mutants and complementation mutants were used as the growth of null mutants were c...
Source: Biochimie - February 25, 2024 Category: Biochemistry Authors: Pradyot Kumar Roy Anindita Paul Sandra Lalchhuanawmi Neerupudi Kishore Babu Sushma Singh Source Type: research

Analysis of differentially expressed proteins in lymph fluids related to lymphatic metastasis in a breast cancer rabbit model guided by contrast ‑enhanced ultrasound
Oncol Lett. 2024 Feb 6;27(4):143. doi: 10.3892/ol.2024.14276. eCollection 2024 Apr.ABSTRACTThe aim of the present study was to identify differentially expressed proteins in the lymph fluid of rabbits with breast cancer lymphatic metastasis compared with healthy rabbits and to analyze and verify these proteins using proteomics technologies. In the process of breast cancer metastasis, the composition of the lymph fluid will also change. Rabbits with breast cancer lymph node metastasis and normal rabbits were selected for analysis. Lymph fluid was extracted under the guidance of percutaneous contrast-enhanced ultrasound. Labe...
Source: Oncology Letters - February 22, 2024 Category: Cancer & Oncology Authors: Jiachao Xu Xin Zhang Guangfei Yang Wei Sun Wen Wang Chengrong Mi Source Type: research

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy
Ann Intern Med. 2024 Feb;177(2):eL230426. doi: 10.7326/L23-0426.NO ABSTRACTPMID:38373321 | DOI:10.7326/L23-0426 (Source: Annals of Internal Medicine)
Source: Annals of Internal Medicine - February 19, 2024 Category: Internal Medicine Authors: Qi Wang Source Type: research