Circulating Concentrations of Vitamin B6 and Kidney Cancer Prognosis: A Prospective Case-Cohort Study

Prospective cohort studies have found that prediagnostic circulating vitamin B6 is inversely associated with both risk of kidney cancer and kidney cancer prognosis. We investigated whether circulating concentrations of vitamin B6 at kidney cancer diagnosis are associated with risk of death using a case-cohort study of 630 renal cell carcinoma (RCC) patients. Blood was collected at the time of diagnosis, and vitamin B6 concentrations were quantified using LC-MS/MS. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. After adjusting for stage, age, and sex, the hazard was 3 times lower among those in the highest compared to the lowest fourth of B6 concentration (HR4vs1 0.33, 95% CI [0.18, 0.60]). This inverse association was solely driven by death from RCC (HR4vs1 0.22, 95% CI [0.11, 0.46]), and not death from other causes (HR4vs1 0.89, 95% CI [0.35, 2.28], p-interaction = 0.008). These results suggest that circulating vitamin B6 could provide additional prognostic information for kidney cancer patients beyond that afforded by tumour stage

Abdominal Adipose Tissue Is Associated With Alterations in Tryptophan-Kynurenine Metabolism and Markers of Systemic Inflammation in People With Human Immunodeficiency Virus

Background: While both adipose tissue accumulation and tryptophan metabolism alterations are features of HIV infection, their interplay is unclear. We investigated associations between abdominal adipose tissue, alterations in kynurenine pathway of tryptophan metabolism, and systemic inflammation in people with HIV (PWH). / Methods: 864 PWH and 75 uninfected controls were included. Plasma samples were collected and analyzed for kynurenine metabolites, neopterin, high-sensitivity CRP (hs-CRP), lipids. Regression models were used to test associations in PWH. / Results: PWH had higher kynurenine-to-tryptophan ratio than uninfected individuals (p-value < 0.001). In PWH, increase in waist-to-hip ratio was associated with higher kynurenine-to-tryptophan ratio (p-value 0.009) and quinolinic-to-kynurenic acid ratio (p-value 0.006) and lower kynurenic acid concentration (p-value 0.019). Quinolinic-to-kynurenic acid ratio was associated with higher hs-CRP (p-value < 0.001) and neopterin concentrations (p-value <0.001), while kynurenic acid was associated with lower hs-CRP (p-value 0.025) and neopterin concentrations (p-value 0.034). / Conclusion: In PWH increase in abdominal adipose tissue was associated with increased quinolinic-to-kynurenic acid ratio, suggesting activation of pro-inflammatory pathway of kynurenine metabolism, with reduction of anti-inflammatory molecules, and increase in systemic inflammation. Our results suggest dysregulation of kynurenine metabolism associated with abdominal fat accumulation to be a potential source of inflammation in HIV infection

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

The reactive species interactome: evolutionary emergence, biological significance, and opportunities for redox metabolomics and personalized medicine

SIGNIFICANCE: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not administration of antioxidants is ineffective, suggesting our current understanding of the underlying regulatory processes is incomplete. Recent Advances. Similar to reactive oxygen and nitrogen species (ROS, RNS), reactive sulfur species (RSS) are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept coined the reactive species interactome (RSI). The RSI is a primeval multi-level redox-regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stresses to enhance fitness and resilience at the local and whole-organism level. CRITICAL ISSUES: To better characterise the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems and effects on cellular, organ and whole-organism bioenergetics using systems-level/network analyses. FUTURE DIRECTIONS: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other stresses will provide new prevention/intervention opportunities for personalized medicine

Effect of betaine supplementation on cycling sprint performance

<p>Abstract</p> <p>Purpose</p> <p>To examine the effect of betaine supplementation on cycling sprint performance.</p> <p>Methods</p> <p>Sixteen recreationally active subjects (7 females and 9 males) completed three sprint tests, each consisting of four 12 sec efforts against a resistance equal to 5.5% of body weight; efforts were separated by 2.5 min of cycling at zero resistance. Test one established baseline; test two and three were preceded by seven days of daily consumption of 591 ml of a carbohydrate-electrolyte beverage as a placebo or a carbohydrate-electrolyte beverage containing 0.42% betaine (approximately 2.5 grams of betaine a day); half the beverage was consumed in the morning and the other half in the afternoon. We used a double blind random order cross-over design; there was a 3 wk washout between trials two and three. Average and maximum peak and mean power were analyzed with one-way repeated measures ANOVA and, where indicated, a Student Newman-Keuls.</p> <p>Results</p> <p>Compared to baseline, betaine ingestion increased average peak power (6.4%; p < 0.001), maximum peak power (5.7%; p < 0.001), average mean power (5.4%; p = 0.004), and maximum mean power (4.4%; p = 0.004) for all subjects combined. Compared to placebo, betaine ingestion significantly increased average peak power (3.4%; p = 0.026), maximum peak power max (3.8%; p = 0.007), average mean power (3.3%; p = 0.034), and maximum mean power (3.5%; p = 0.011) for all subjects combined. There were no differences between the placebo and baseline trials.</p> <p>Conclusions</p> <p>One week of betaine ingestion improved cycling sprint power in recreationally active males and females.</p

Normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia are associated with similiar risks of cardiovascular events in patients with premature peripheral arterial occlusive disease. A prospective cohort study

Objectives. Mild hyperhomocysteinaemia (HHC), fasting or after methionine loading, is associated with an increased risk and severity of atherosclerotic vascular disease. Post-methionine and fasting HHC are responsive to treatment with vitamin

Serum levels of osteoprotegerin and receptor activator of nuclear factor -κB ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study

<p>Abstract</p> <p>Background</p> <p>The clinical relevance of observations of serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor -κB ligand (RANKL) in juvenile idiopathic arthritis (JIA) is not clear. To elucidate the potential role of OPG and RANKL in JIA we determined serum levels of OPG and RANKL in patients with early JIA compared to healthy children, and prospectively explored changes in relation to radiographic score, bone and lean mass, severity of the disease, and treatment.</p> <p>Methods</p> <p>Ninety children with early oligoarticular or polyarticular JIA (ages 6-18 years; mean disease duration 19.4 months) and 90 healthy children individually matched for age, sex, race, and county of residence, were examined at baseline and 2-year follow-up. OPG and RANKL were quantified by enzyme-immunoassay. Data were analyzed with the use of t-tests, ANOVA, and multiple regression analyses.</p> <p>Results</p> <p>Serum OPG was significantly lower in patients than controls at baseline, and there was a trend towards higher RANKL and a lower OPG/RANKL ratio. Patients with polyarthritis had significantly higher increments in RANKL from baseline to follow-up, compared to patients with oligoarthritis. RANKL was a significant negative predictor for increments in total body lean mass. Patients who were receiving corticosteroids (CS) or disease-modifying antirheumatic drugs (DMARDs) at follow-up had higher OPG/RANKL ratio compared with patients who did not receive this medication.</p> <p>Conclusions</p> <p>The data supports that levels of OPG are lower in patients with JIA compared to healthy children, and higher levels of RANKL is associated with more serious disease. RANKL was a significant negative predictor of lean mass in patients with JIA. The OPG/RANKL ratio was higher in patients on DMARDs or CS treatment.</p

Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Previous studies have suggested that components of one-carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case-control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5'-phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these association were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared with high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. This article is protected by copyright. All rights reserved

Serum homocysteine, vitamin B 12 and folic acid levels in different types of glaucoma

BACKGROUND: This study was performed to compare levels of serum homocysteine (Hcy), vitamin B12 and folic acid in patients with primary open-angle glaucoma (POAG), pseudoexfoliative glaucoma (PEXG), normotensive glaucoma (NTG) and healthy controls. METHODS: Twentyfive patients with POAG, 24 with PEXG, and 18 with NTG, along with 19 control healthy subjects were included this prospective study. Levels of serum Hcy were measured using immunoassay, and those of serum vitamin B12 and folic acid were measured using competitive chemiluminescent enzyme immunoassay. RESULTS: The mean Hcy concentration in the PEXG group was significantly higher (P < 0.001) as compared to the other groups. There were no significant differences with respect to the mean Hcy concentrations among other groups (P > 0.05). There were no statistical differences in serum vitamin B12 levels among POAG, PEXG, NTG and control subjects (P > 0.05). The mean serum folic acid level was significantly lower in the subjects with PEXG (P < 0.009). However, the mean folic acid concentrations among the other groups did not differ significantly (P > 0.05). CONCLUSION: Elevated levels of Hcy in PEXG may explain the role of endothelial dysfunction among patients with PEXG