scholarly journals Molecular Phenotyping of Oxidative Stress in Diabetes Mellitus with Point-of-care NMR system

2019 ◽  
Author(s):  
Weng Kung Peng ◽  
Lan Chen ◽  
Bernhard O Boehm ◽  
Jongyoon Han ◽  
Tze Ping Loh

AbstractDiabetes mellitus is one of the fastest growing health burdens globally. Oxidative stress which has been implicated to the pathogenesis of diabetes complication (e.g., cardiovascular event) were, however, poorly understood. We report a novel approach to rapidly manipulate the redox chemistry (in a single drop) of blood using point-of-care NMR system. We exploit the fact that oxidative stress changes the subtle molecular motion of water-proton in the blood, and thus inducing a measurable shift in magnetic resonance relaxation properties. This technique is label-free and the whole assays finish in a few minutes. Various redox states of the hemoglobin were mapped out using our newly proposed two-dimensional map, known as T1-T2 magnetic state diagram. We demonstrated the clinical utilities of this technique to rapidly sub-stratify diabetes subjects based on their oxidative status (in conjunction to the traditional glycemic level), to improve the patient risk stratification and thus the overall outcome of clinical diabetes care and management. (155 words)Key Points for SummariesA novel approach to rapidly manipulate the redox chemistry (in a single drop) of blood using point-of-care NMR system.Assessment of the oxidative status, in conjunction to their glycemic level allows sub-stratification of diabetes subjects which was demonstrated clinically.Visual Abstract

Author(s):  
Weng Kung Peng ◽  
Lan Chen ◽  
Bernhard O. Boehm ◽  
Jongyoon Han ◽  
Tze Ping Loh

Abstract Diabetes mellitus is one of the fastest-growing health burdens globally. Oxidative stress, which has been implicated in the pathogenesis of diabetes complication (e.g., cardiovascular event), remains poorly understood. We report a new approach to rapidly manipulate and evaluate the redox states of blood using a point-of-care NMR system. Various redox states of the hemoglobin were mapped out using the newly proposed (pseudo) two-dimensional map known as T1–T2 magnetic state diagram. We exploit the fact that oxidative stress changes the subtle molecular motion of water proton in the blood, and thus inducing a measurable shift in magnetic resonance relaxation properties. We demonstrated the clinical utilities of this technique to rapidly stratify diabetes subjects based on their oxidative status in conjunction to the traditional glycemic level to improve the patient stratification and thus the overall outcome of clinical diabetes care and management.


2021 ◽  
Vol 99 (2) ◽  
pp. 121-127
Author(s):  
S. S. Popov ◽  
E. I. Anufrieva ◽  
E. D. Krylskiy ◽  
K. K. Shulgin ◽  
A. N. Verevkin ◽  
...  

Chronic kidney disease (CKD) is the main cause of end-stage renal failure and is a complication of diabetes mellitus (DM). Oxidative stress plays the key role in its pathogenesis. In this regard, the use of drugs with antioxidant effect in DN therapy seems to be reasonable.Objective. In the course of this work, the effect of combination melatonin therapy on the biochemical parameters of the pathology development, concentration of pigment epithelial factor (PEDF) and the oxidative status of patients with CKD developing in type II diabetes was assessed.Material and methods. The study involved 60 people with CKD developing in type II diabetes. The patients were divided into 2 groups; each group included 30 people. The first group of patients underwent basic treatment; the second group of participants was given 2 mg of melatonin in addition to the basic therapy. The control group consisted of 65 apparently healthy individuals with normal indicators of general and biochemical blood tests. In the course of the work, the analysis of biochemical indicators of the pathology development, level of PEDF by enzyme immunoassay, the activity of free radical oxidation by the method of iron-induced biochemiluminescence (BCL) and the concentration of reduced glutathione (GSH) in the study participants was carried out.Results. The addition of melatonin to basic treatment led to a more signifi cant decrease in the intensity of free radical-induced oxidation and the level of PEDF, as well as an increase in the GSH content and general antioxidant eff ect in patients with CKD. The observed changes were accompanied by shifts in the indicators of proteinuria, hyperglycemia and urea concentration close to the ones detected in healthy volunteers group.Conclusion. The results obtained were, apparently, due to a more signifi cant decrease in the level of oxidative stress in patients who additionally received melatonin, which is characterized by the presence of antioxidant activity. An improvement in the oxidative status in patients of the second group was linked with the degree of changes in the clinical and biochemical parameters of pathology.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10776
Author(s):  
Laongthip Ruknarong ◽  
Chongchira Boonthongkaew ◽  
Nisa Chuangchot ◽  
Amonrat Jumnainsong ◽  
Naruemon Leelayuwat ◽  
...  

Background Vitamin C is an essential element required for normal metabolic function. We investigated the effect of vitamin C supplementation on circulating miRNA (miR) expression in subjects with poorly controlled type 2 diabetes mellitus (T2DM). Changes in miR expression were also correlated with clinical measures of disease. Methods Pre- and post-vitamin C supplementation samples from five participants who had increased vitamin C levels, improved oxidative status and polymorphonuclear (PMN) function after receiving 1,000 mg of vitamin C daily for six weeks were screened for miRNA expression using the NanoString miRNA assay. Differences in miRNA expression identified from the miRNA screen were validated by qRT-PCR. Results Four miRNAs showed significantly different expression post-vitamin C supplementation relative to baseline, including the down-regulation of miR-451a (−1.72 fold change (FC), p = 0.036) and up-regulation of miR-1253 (0.62 FC, p = 0.027), miR-1290 (0.53 FC, p = 0.036) and miR-644a (0.5 FC, p = 0.042). The validation study showed only miR-451a expression was significantly different from baseline with vitamin C supplementation. MiR-451a expression was negatively correlated with vitamin C levels (r =  − 0.497, p = 0.049) but positively correlated with levels of malondialdehyde (MDA) (r = 0.584, p = 0.017), cholesterol (r = 0.564, p = 0.022) and low-density lipoproteins (LDL) (r = 0.522, p = 0.037). Bioinformatics analysis of the putative target genes of miR-451a indicated gene functions related to signaling pathways involved in cellular processes, such as the mammalian target of rapamycin (mTOR) signaling pathway. Conclusions Vitamin C supplementation altered circulating miR-451a expression. The results from this pilot study suggest that miRNAs could be used as biomarkers to indicate oxidative status in subjects with T2DM and with poor glycemic control and could lead to a novel molecular strategy to reduce oxidative stress in T2DM.


Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1753
Author(s):  
Anne Lee Solevåg ◽  
Svetlana N. Zykova ◽  
Per Medbøe Thorsby ◽  
Georg M. Schmölzer

There is a need for feasible and non-invasive diagnostics in perinatal asphyxia. Metabolomics is the study of small molecular weight products of cellular metabolism that may, directly and indirectly, reflect the level of oxidative stress. Saliva analysis is a novel approach that has a yet unexplored potential in metabolomics in perinatal asphyxia. The aim of this review was to give an overview of metabolomics studies of oxidative stress in perinatal asphyxia, particularly searching for studies analyzing non-invasively collected biofluids including saliva. We searched the databases PubMed/Medline and included 11 original human and 4 animal studies. In perinatal asphyxia, whole blood, plasma, and urine are the most frequently used biofluids used for metabolomics analyses. Although changes in oxidative stress-related salivary metabolites have been reported in adults, the utility of this approach in perinatal asphyxia has not yet been explored. Human and animal studies indicate that, in addition to antioxidant enzymes, succinate and hypoxanthine, as well acylcarnitines may have discriminatory diagnostic and prognostic properties in perinatal asphyxia. Researchers may utilize the accumulating evidence of discriminatory metabolic patterns in perinatal asphyxia to develop bedside methods to measure oxidative stress metabolites in perinatal asphyxia. Although only supported by indirect evidence, saliva might be a candidate biofluid for such point-of-care diagnostics.


2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.


2014 ◽  
Author(s):  
Cristina Lopez-Tinoco ◽  
Francisco Vilchez ◽  
Francisco Visiedo ◽  
Isabel Mateo ◽  
Carmen Segundo ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 908-P
Author(s):  
SOSTENES MISTRO ◽  
THALITA V.O. AGUIAR ◽  
VANESSA V. CERQUEIRA ◽  
KELLE O. SILVA ◽  
JOSÉ A. LOUZADO ◽  
...  

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