Colorimetric array sensor based on bimetallic nitrogen-doped carbon-based nanozyme material to detect multiple antioxidants.

Copper-cobalt bimetallic nitrogen-doped carbon-based nanoenzymatic materials (CuCo@NC) were synthesized using a one-step pyrolysis process. A three-channel colorimetric sensor array was constructed for the detection of seven antioxidants, including cysteine (Cys), uric acid (UA), tea polyphenols (TP), lysine (Lys), ascorbic acid (AA), glutathione (GSH), and dopamine (DA). CuCo@NC with peroxidase activity was used to catalyze the oxidation of TMB by H2O2 at three different ratios of metal sites. The ability of various antioxidants to reduce the oxidation products of TMB (ox TMB) varied, leading to distinct absorbance changes. Linear discriminant analysis (LDA) results showed that the sensor array was capable of detecting seven antioxidants in buffer and serum samples. It could successfully discriminate antioxidants with a minimum concentration of 10 nM. Thus, multifunctional sensor arrays based on CuCo@NC bimetallic nanoenzymes not only offer a promising strategy for identifying various antioxidants but also expand their applications in medical diagnostics and environmental analysis of food.

Atomically Co-dispersed nitrogen-doped carbon for sensitive electrochemical immunoassay of breast cancer biomarker CA15-3.

The development of an ultrasensitive and precise measurement of a breast cancer biomarker (cancer antigen 15-3; CA15-3) in complex human serum is essential for the early diagnosis of cancer in groups of healthy populations and the treatment of patients. However, currently available testing technologies suffer from insufficient sensitivity toward CA15-3, which severely limits early large-scale screening of breast cancer patients. We report a versatile electrochemical immunoassay method based on atomically cobalt-dispersed nitrogen-doped carbon (Co-NC)-modified disposable screen-printed carbon electrode (SPCE) with alkaline phosphatase (ALP) and its metabolite, ascorbic acid 2-phosphate (AAP), as the electrochemical labeling and redox signaling unit for sensitive detection of low-abundance CA15-3. During electrochemical detection by differential pulse voltammetry (DPV), it was found that the Co-NC-SPCE electrode did not have a current signal response to the AAP substrate; however, it had an extremely favorable response current to ascorbic acid (AA). Based on the above principle, the target CA15-3-triggered immunoassay enriched ALP-catalyzed AAP produces a large amount of AA, resulting in a significant change in the system current signal, thereby realizing the highly sensitive detection of CA15-3. Under the optimal AAP substrate concentration and ALP catalysis time, the Co-NC-SPCE-based electrochemical immunoassay demonstrated a good DPV current for CA15-3 in the assay interval of 1.0 mU/mL to 10,000 mU/mL, with a calculated limit of detection of 0.38 mU/mL. Since Co-NC-SPCE has an excellent DPV current response to AA and employs split-type scheme, the constructed electrochemical immunoassay has the merits of high preciseness and anti-interference, and its clinical diagnostic results are comparable to those of commercial kits.

The effect of solarium light therapy on selected biological and biochemical parameters of peripheral blood in young and old horses.

The aim of the study was to assess the impact of solarium light therapy on selected biological and biochemical parameters of peripheral blood in recreational horses. The study involved 10 horses divided into two groups of young (aged 5 to 7 years) and old (aged 14 to 19 years) individuals. All animals participated in light therapy sessions every other day. Blood was sampled three times during the study: before the treatment, after five light sessions, and after ten light sessions. Morphological parameters, the activity of antioxidant enzymes, TAS values, and the levels of glutathione (GSH), vitamin D3, vitamin C, and malondialdehyde (MDA) were measured in the whole blood. Light therapy contributed to an increase in MCV, HDW, MCVr, CHr and MPV indices, and simultaneously a decrease in the basophil counts, MCHC, RDW and CHCMr indices in both groups of horses (p ≤ 0.05). At the same time reticulocytes fell in older whereas white blood cells and monocytes counts expanded in younger individuals. The treatment also increased the activity of glutathione reductase (GR) and glutathione peroxidase (GPx) in young but decreased the activity of mentioned enzymes in blood plasma of old horses. The total antioxidant status (TAS) of the blood plasma rose progressively, whereas GSH levels declined in all individuals. Moreover, vitamin D3 levels did not change, whereas vitamin C levels gradually decreased during the experiment. The therapy also helped to reduce levels of MDA in the blood plasma, especially of older horses (p ≤ 0.05). In turn, GPx and GR activities as well as MDA levels significantly declined, whereas GSH levels notably elevated in erythrocytes (p ≤ 0.05). Solarium light therapy appears to have a beneficial impact on the morphological parameters and antioxidant status of blood in recreational horses in the winter season. However, the observed results could in part be attributed to the natural physiological adaptation of each individual organism to the treatment.

Detection of alkaline phosphatase activity with a CsPbBr3/Y6 heterojunction-based photoelectrochemical sensor.

An ultra-sensitive photoelectrochemical (PEC) sensor based on perovskite composite was developed for the determination of alkaline phosphatase (ALP) in human serum. In contrast to CsPbBr3 or Y6 that generated anodic current, the heterojunction of CsPbBr3/Y6 promoted photocarriers to separate and generated cathodic photocurrent. Ascorbic acid (AA) was produced by ALP hydrolyzing L-ascorbic acid 2-phosphate trisodium salt (AAP), which can combine with the holes on the photoelectrode surface, accelerating the transmission of photogenerated carriers, leading to enhanced photocurrent intensity. Thus, the enhancement of PEC current was linked to ALP activity. The PEC sensor exhibits good sensitivity for detection of ALP owing to the unique photoelectric properties of the CsPbBr3/Y6 heterojunction. The detection limit of the sensor was 0.012 U·L-1 with a linear dynamic range of 0.02-2000 U·L-1. Therefore, this PEC sensing platform shows great potential for the development of different PEC sensors.

Association between vitamin C in serum and trouble sleeping based on NHANES 2017-2018.

Vitamin C is an important micronutrient for human. Association between vitamin C and trouble sleeping was less studied. Therefore, the purpose of this study was to investigate the possible link between vitamin C in serum and trouble sleeping. The cross-sectional data was derived from the National Health and Nutrition Examination Survey (NHANES, 2017-2018). Trouble sleeping was measured by asking participants: "Have you ever told doctor had trouble sleeping". Responses to this question was "yes" or "no". vitamin C in serum was obtained by measuring the serum samples. We used multivariable binary logistic regressions to examine the possible link between vitamin C in serum and trouble sleeping, and then a subgroup analysis was performed. Moreover, the non-linear relationship between vitamin C in serum and trouble sleeping was further detected using a restricted cubic spline (RCS) model. A total of 3227 participants were included in the study. After adjusting all potential confounders, the results of multivariable logistic regression showed the significant negative association between vitamin C in serum and trouble sleeping(OR = 0.816; 95% CI:0.669 ~ 0.995). The significant inverse association was also found in female(OR = 0.713; 95% CI:0.546 ~ 0.931), age ≤ 65 years(OR = 0.773; 95% CI:0.600 ~ 0.996), and in participants with high cholesterol level(OR = 0.738; 95% CI:0.548 ~ 0.994). In addition, the RCS model demonstrated the significant non-linear relationship between vitamin C in serum and trouble sleeping (P value of nonlinear = 0.010). Our study demonstrates the significant negative association between vitamin C in serum and trouble sleeping.

Phosphorus Modulated Peroxidase-Like Activity of Carbon Dots for Colorimetric Detection of Acid Phosphatase.

The precise regulation of nanoenzyme activity is of great significance for application to biosensing analysis. Herein, the peroxidase-like activity of carbon dots was effectively modulated by doping phosphorus, which was successfully employed for sensitive, selective detection of acid phosphatase (ACP). Phosphorus-doped carbon dots (P-CDs) with excellent peroxidase-like activity were synthesized by a one-pot hydrothermal method, and the catalytic activity could be easily modulated by controlling the additional amount of precursor phytic acid. P-CDs could effectively catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB oxidation products in the presence of hydrogen peroxide. While ACP was able to catalyze the hydrolysis of L-ascorbyl-2-phosphate trisodium salt (AAP) to produce ascorbic acid (AA), which inhibited the peroxidase-like activity of P-CDs, by combining P-CDs nanoenzymes and ACP-catalyzed hydrolysis the colorimetric method was established for ACP detection. The absorbance variation showed a good linear relationship with ACP concentration in the range of 0.4-4.0 mU/mL with a limit of detection at 0.12 mU/mL. In addition, the method was successfully applied to detect ACP in human serum samples with recoveries in the range of 98.7-101.6%. The work provides an effective strategy for regulating nanoenzymes activity and a low-cost detection technique for ACP.

A ratiometric fluorescent probe for simultaneous detection of L-ascorbic acid and alkaline phosphatase activity based on red carbon dots/polydopamine nanocomposite.

Herein, efficient red carbon dots (R-CDs) were synthesized by one-step hydrothermal treatment of N-(4-amino phenyl) acetamide and (2,3-difluoro phenyl) boronic acid. The optimal emission peak of R-CDs was at 602 nm (under 520 nm excitation) and the absolute fluorescence quantum yield of R-CDs was 12.9%. Polydopamine, which was formed by the self-polymerization and cyclization of dopamine in alkaline condition, emitted characteristic fluorescence with peak position of 517 nm (under 420 nm excitation) and affected the fluorescence intensity of R-CDs through inner filter effect. L-Ascorbic acid (AA), which was the hydrolysis product of L-ascorbic acid-2-phosphate trisodium salt under the catalytic reaction of alkaline phosphatase (ALP), effectively prevented the polymerization of dopamine. Combined with the ALP-mediated AA production and the AA-mediated polydopamine generation, the ratiometric fluorescence signal of polydopamine with R-CDs was correlated closely with the concentration of both AA and ALP. Under optimal conditions, the detection limits of AA and ALP were 0.28 µM during linear range of 0.5-30 µM and 0.044 U/L with linear range of 0.05-8 U/L, respectively. This ratiometric fluorescence detection platform can efficiently shield the background interference of sophisticated samples by introducing a self-calibration as reference signal in a multi-excitation mode, which can detect AA and ALP in human serum samples with satisfactory results. Such R-CDs/polydopamine nanocomposite provides a steadfast quantitative information and makes R-CDs be excellent candidate for biosensors via combining target recognition strategy.

Genetically predicted circulating vitamin C in relation to cardiovascular disease.

AIM: We conducted a two-sample Mendelian randomization (MR) study to assess the associations of genetically predicted circulating vitamin C levels with cardiovascular diseases (CVDs). METHODS AND RESULTS: Ten lead single-nucleotide polymorphisms associated with plasma vitamin C levels at the genome-wide significance level were used as instrumental variables. Summary-level data for 15 CVDs were obtained from corresponding genetic consortia, the UK Biobank study, and the FinnGen consortium. The inverse-variance-weighted method was the primary analysis method, supplemented by the weighted median and MR-Egger methods. Estimates for each CVD from different sources were combined. Genetically predicted vitamin C levels were not associated with any CVD after accounting for multiple testing. However, there were suggestive associations of higher genetically predicted vitamin C levels (per 1 standard deviation increase) with lower risk of cardioembolic stroke [odds ratio, 0.79; 95% confidence interval (CI), 0.64, 0.99; P = 0.038] and higher risk of atrial fibrillation (odds ratio, 1.09; 95% CI, 1.00, 1.18; P = 0.049) in the inverse-variance-weighted method and with lower risk of peripheral artery disease (odds ratio, 0.76, 95% CI, 0.62, 0.93; P = 0.009) in the weighted median method. CONCLUSION: We found limited evidence with MR techniques for an overall protective role of vitamin C in the primary prevention of CVD. The associations of vitamin C levels with cardioembolic stroke, atrial fibrillation, and peripheral artery disease need further study.

Ascorbic acid detector based on fluorescent molybdenum disulfide quantum dots.

A rapid and facile method is reported for the detection of ascorbic acid using molybdenum disulfide quantum dots (MoS2 QDs) as a fluorescence sensor. Water-soluble and biocompatible MoS2 QDs with the maximum fluorescence emission at 506 nm have been successfully synthesized by hydrothermal method and specific detection for ascorbic acid (AA) was constructed to utilize the modulation of metal ion on the fluorescence of MoS2 QDs and the affinity and specificity between the ligand and the metal ion. The fluorescence of MoS2 QDs was quenched by the irreversible static quenching of Fe3+ through the formation of a MoS2 QDs/Fe3+ complex, while the pre-existence of AA can retain the fluorescence of MoS2 QDs through the redox reaction between AA and Fe3+. Based on this principle, a good linear relationship was obtained in the AA concentration range 1 to 150 µM with a detection limit of 50 nM. The proposed fluorescent sensing strategy was proven to be highly selective, quite simple, and rapid with a requirement of only 5 min at room temperature (RT), which is particularly useful for rapid and easy analysis. Satisfactory results were obtained when applied to AA determination in fruits, beverages, and serum samples as well as AA imaging in living cells, suggesting its great potential in constructing other fluorescence detection and imaging platforms.

Insufficient Vitamin C Levels among Adults in the United States: Results from the NHANES Surveys, 2003-2006.

Vitamin C, well-established in immune function and a key factor in epigenetic inflammatory modifications, is only obtained through consistent dietary intake. Identifying individuals at risk for Vitamin C insufficiency may guide prevention and treatment, however, national surveillance has not been evaluated in the United States since 2006. A descriptive, cross-sectional secondary analysis was performed utilizing data from the 2003-2006 National Health and Nutrition Examination Surveys (NHANES) assessing non-institutionalized adults. Five categories of plasma Vitamin C were delineated: deficiency (<11 µmol/L), hypovitaminosis (11-23 µmol/L), inadequate (23-49 µmol/L), adequate (50-69 µmol/L), and saturating (≥70 µmol/L). Results indicated 41.8% of the population possessed insufficient levels (deficiency, hypovitaminosis, and inadequate) of Vitamin C. Males, adults aged 20-59, Black and Mexican Americans, smokers, individuals with increased BMI, middle and high poverty to income ratio and food insecurity were significantly associated with insufficient Vitamin C plasma levels. Plasma Vitamin C levels reveal a large proportion of the population still at risk for inflammatory driven disease with little to no symptoms of Vitamin C hypovitaminosis. Recognition and regulation of the health impact of Vitamin C support the goal of Nutrition and Healthy Eating as part of the Healthy People 2030.

Vitamins as Possible Cancer Biomarkers: Significance and Limitations.

The Western-style diet, which is common in developed countries and spreading into developing countries, is unbalanced in many respects. For instance, micronutrients (vitamins A, B complex, C, D, E, and K plus iron, zinc, selenium, and iodine) are generally depleted in Western food (causing what is known as 'hidden hunger'), whereas some others (such as phosphorus) are added beyond the daily allowance. This imbalance in micronutrients can induce cellular damage that can increase the risk of cancer. Interestingly, there is a large body of evidence suggesting a strong correlation between vitamin intake as well as vitamin blood concentrations with the occurrence of certain types of cancer. The direction of association between the concentration of a given vitamin and cancer risk is tumor specific. The present review summarized the literature regarding vitamins and cancer risk to assess whether these could be used as diagnostic or prognostic markers, thus confirming their potential as biomarkers. Despite many studies that highlight the importance of monitoring vitamin blood or tissue concentrations in cancer patients and demonstrate the link between vitamin intake and cancer risk, there is still an urgent need for more data to assess the effectiveness of vitamins as biomarkers in the context of cancer. Therefore, this review aims to provide a solid basis to support further studies on this promising topic.

Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study.

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case-control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05-3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05-5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58-6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.

The impact of plasma vitamin C levels on the risk of cardiovascular diseases and Alzheimer's disease: A Mendelian randomization study.

BACKGROUND & AIMS: Previous observational studies have reported associations between plasma vitamin C levels, and cardiovascular diseases (CVDs) and Alzheimer's disease (AD); however, no conclusive results have been obtained. We conducted a Mendelian randomization (MR) study to investigate the causality of vitamin C on the risk of nine CVDs [including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes] and Alzheimer's disease. METHODS: Eleven single-nucleotide polymorphisms (SNPs) identified in a recent genome-wide meta-analysis (N = 52,018) were used as the instrumental variables for plasma vitamin C levels. The summary-level data for CVDs and AD were extracted from consortia and genome-wide association studies (GWAS). We performed MR analyses using the fixed-effects inverse-variance-weighted (IVW) method, weighted median, and MR-Egger approaches. RESULTS: This MR study found suggestive evidence that genetic liability to higher vitamin C levels was associated with a lower risk of cardioembolic stroke [odds ratio (OR, presented per 1 standard deviation increase in plasma vitamin C levels) = 0.773; 95% confidence interval (CI), 0.623-0.959; P = 0.020] and AD (OR = 0.968; 95% CI, 0.946-0.991; P = 0.007) using the fixed-effects IVW method. Sensitivity analysis yielded directionally similar results. A null-association was observed between vitamin C and the other CVDs. CONCLUSION: Our MR study provided suggestive evidence that higher vitamin C levels were casually associated with a decreased risk of cardioembolic stroke and AD. No evidence was observed to suggest that vitamin C affected the risk of CAD, MI, AF, HF, stroke, IS, large artery stroke, or small vessel stroke. However, well-designed studies are warranted to confirm these results and determine the underlying mechanisms of the causal links.

Serum Micronutrients as related to Childhood Pneumonia Severity and Outcome in a Nigerian Health Facility.

INTRODUCTION: Micronutrients are essential minerals and vitamins needed for optimal health. There are however conflicting reports about the roles of micronutrients in severity and outcomes of childhood pneumonia. This study aims to determine the socio-demographic and serum micronutrients - Zinc (Zn), Selenium (Se), Vitamins (Vit) A, C and E status of Nigerian children with or without pneumonia and relate these to pneumonia severity and outcome. METHODOLOGY: Children aged two months to 14 years with severe and non-severe pneumonia were recruited with age and sex-matched controls over 12 month period in a Nigerian tertiary health centre. Relevant history and serum micronutrients were compared in the two groups and related to pneumonia severity and length of hospitalisation (LOH). RESULTS: One hundred and forty-four children (72 for each group) were recruited with median (IQR) age 1.6 (0.6 - 4.0) years and fifty-six (38.8%) had severe pneumonia. Pneumonia incidence was associated with undernutrition, inappropriate immunisation and Zn deficiency (p < 0.05). Hypovitaminosis A [60.8(22.2)µg/dl vs. 89.5(34.7)µg/dl; p < 0.001], low serum Zn [71.6(32.5)µg/dl vs. 92.6(24.6)µg/dl; p=0.019] and indoor air pollution (IAP) were associated with pneumonia severity. However, only IAP (OR = 4.529; 95%CI 1.187-17.284; p=0.027) and Zn deficiency (OR=6.144; 95%CI 1.157-32.617; p=0.033) independently predicted severe pneumonia. No significant correlation between serum micronutrients and LOH. CONCLUSIONS: Exposure to IAP and low serum micronutrients particularly Zn and Vit A were associated with pneumonia incidence and severity in Nigerian children. Routine micronutrient supplementation may assist to reduce the burden of childhood pneumonia in developing countries.

Measuring vitamin C in critically ill patients: clinical importance and practical difficulties-Is it time for a surrogate marker?

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review.

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

Excessively low cholesterol and triglyceride levels in an apparently healthy patient.

Lipid panels are a commonly performed test in clinical laboratories. Due to the high prevalence of cardiovascular diseases around the world, it is common to see serum or plasma specimens with high results for one or more components of the lipid panel. Exceedingly low results, however, are rare and may be attributed to certain genetic, infectious, or autoimmune conditions in addition to analytical interference. Here we report a serum specimen from a 58-year-old female with cholesterol and triglyceride values below the detection limit of the assay, which was investigated to identify the cause of the anomaly. Using vitamin C test strips and high-performance liquid chromatography, the presence of high levels of antioxidant vitamin C in the patient specimen was confirmed. Subsequent treatment of the sample with the enzyme ascorbate oxidase inactivated vitamin C, leading to lipid analyte values falling within the expected range upon repeat analysis. Thus, analytical interference by vitamin C should be considered when suspiciously low lipid panel results are encountered.

COVID-19: Up to 82% critically ill patients had low Vitamin C values.

There are limited proven therapeutic options for the prevention and treatment of COVID-19. We underwent an observational study with the aim of measure plasma vitamin C levels in a population of critically ill COVID-19 adult patients who met ARDS criteria according to the Berlin definition. This epidemiological study brings to light that up to 82% had low Vitamin C values. Notwithstanding the limitation that this is a single-center study, it nevertheless shows an important issue. Given the potential role of vitamin C in sepsis and ARDS, there is gathering interest of whether supplementation could be beneficial in COVID-19.