Mazyar Yazdani

@ous-research.no

Department of Medical Biochemistry
Oslo University Hospital



                             

https://researchid.co/mazyar.yazdani.edu

Dr. Yazdani’s research journey began in toxicology, where he studied the mechanisms by which hazardous substances induce oxidative stress and developed in vitro (cell culture) models to examine these effects. His focus later shifted to exploring the role of oxidative stress in the pathophysiology of dry eye disease and potential treatments for corneal epithelial (limbal) stem cell deficiency. Currently, as a core member of the Metabolomics & Metabolic Molecular Biology group, he investigates the impact of metabolic changes on health and disease, with the goal of understanding disease mechanisms through mass spectrometry-based metabolomics. Additionally, he has maintained a strong interest in the biological role and effects of oxygen.

EDUCATION

2009-2014: PhD in Integrative Biology - Toxicology, University of Oslo, Norway

Committee: Ketil Hylland , Ragnhild Paulsen & Tor Gjøen
Collaborator: Gunnar Brunborg at the Norwegian Institute of Public Health
Trial lecture: Mechanisms for endocrine disruption
Thesis: In vitro, in ovo and in vivo models for cytotoxicity, oxidative stress, neurotoxicity and DNA damage ( Link )

RESEARCH, TEACHING, or OTHER INTERESTS

Biochemistry, Molecular Biology, Molecular Medicine, Health, Toxicology and Mutagenesis

38

Scopus Publications

996

Scholar Citations

17

Scholar h-index

21

Scholar i10-index

Scopus Publications

  • Tear Global Metabolomic Differences in Pre-Operative Cataract Patients With and Without Dry Eye Disease
    Morten Gundersen, Christian Nilsen, Per Jensen, Mazyar Yazdani, Øygunn Utheim, Elise Sandås Sand, Helge Rootwelt, Kjell Gunnar Gundersen, and Katja Benedikte Prestø Elgstøen
    Informa UK Limited
    PURPOSE The primary aim of this article was to investigate differences in the metabolomic profile of tear fluid obtained from pre-operative cataract patients, with or without dry eye disease. The objective was to look for metabolomic signatures that might discriminate between the two groups. METHODS A total of 222 patients were enrolled in the study. Eighty-one were randomly selected for metabolomic analysis from both dry eye positive and dry eye negative groups, categorized prior to cataract surgery. Tear film was collected using Schirmer-1 strips and analyzed using an optimized method developed for low-volume Schirmer samples and allowing for repeated analyses, including other -omics approaches at a later stage. Metabolomic data were collected using a global liquid chromatography-mass spectrometry method. Samples were compared using principal component analysis and volcano plots to look for overall global differences as well as group-specific metabolic signatures. RESULTS All samples were analyzed with a high number of features identified. No group-specific clustering was observed in principal component analysis for the dry eye positive or dry eye negative groups. However, volcano plots revealed that a majority of the metabolomic features had lower concentration in the dry eye positive group compared to the dry eye negative group. Four of these features had a Log2-fold change ≤ -1 and p value ≤.05. These warrant further study. CONCLUSION Although no overall global difference was observed on the principal component analysis plots, a general trend of lower metabolite concentrations in the dry eye disease group was shown. Moreover, several metabolites of interest were discovered with significantly different signal intensities between the groups. These metabolites may aid future diagnostics and serve as possible biomarkers and therapeutic targets for dry eye disease in pre-operative cataract patients.


  • Can endogenous ethylene glycol production occur in humans? A detailed investigation of adult monozygotic twin sisters
    Marc Ghannoum, Paula J. Waters, Knut Erik Hovda, Gabrielle Choquette, Katja Benedikte Prestø Elgstøen, Ilah Nygaard, Helge Rootwelt, Dean Hickey, Mazyar Yazdani, and Danielle K. Bourque
    Informa UK Limited
    INTRODUCTION To the best of our knowledge, clinically significant endogenous ethylene glycol production has never been reported in humans, very seldom reported in other animals or microorganisms, and then only under rare and specific conditions. We describe the detailed investigations we undertook in two adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol. METHODS Two previously healthy monozygotic adult twin sisters presented with recurrent episodes of apparent ethylene glycol poisoning beginning at age 35, requiring chronic hemodialysis to remove ethylene glycol and its metabolites as well as to restore metabolic homeostasis. The sisters denied ingestion or exposure to ethylene glycol. At their request, they were admitted to hospital under strict supervision to exclude surreptitious ingestion of ethylene glycol and to evaluate the need for treatment. Hemodialysis was withheld during this prospective study. Twin A was admitted for 14 days and twin B for 11 days. Serial biochemical analyses were performed in blood and urine. Clinical exome sequencing and mitochondrial deoxyribonucleic acid sequencing were also completed. RESULTS In both twins, ethylene glycol was detected in urine, along with intermittent increases in concentrations of lactate, glycolate, and glycine in blood and/or urine. Blood ethylene glycol concentrations, however, remained <62 mg/L (<1 mmol/L) but became positive soon after discharge. The oxalate concentration remained normal in blood and urine. Plasma and urine amino acid profiles showed intermittent small increases in glycine, serine, taurine, proline, and/or alanine concentrations. Exome sequencing and mitochondrial deoxyribonucleic acid sequencing were non-diagnostic. Neither twin has been admitted with metabolic acidosis nor ethylene glycol poisoning since chronic hemodialysis was started. Twin A developed a calcium oxalate dihydrate lithiasis. DISCUSSION Mitochondrial disease, methylmalonic/propionic/isovaleric aciduria, primary hyperoxaluria, and analyte error were all excluded in these twins, as were obvious common environmental exposures. CONCLUSION Detailed investigations were performed in adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol. Alternative explanations were excluded to the very best of our efforts and knowledge. Global metabolomics, gut microbiome analyses, and whole genome sequencing are pending.

  • Iron Metabolism, Calcium, Magnesium and Trace Elements: A Review
    Tara Rolić, Mazyar Yazdani, Sanja Mandić, and Sonia Distante
    Springer Science and Business Media LLC
    AbstractIron (Fe) is fundamental to life on earth. In the human body, it is both essential and harmful if above threshold. A similar balance applies to other elements: calcium (Ca), magnesium (Mg), and trace elements including copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), mercury (Hg), and nickel (Ni). These elements share some proteins involved in the absorption and transport of Fe. Cu and Cd can inhibit Fe absorption, while excess of Fe may antagonize Cu metabolism and reduce ceruloplasmin (Cp). Excessive Fe can hinder Zn absorption and transferrin (Trf) can bind to both Zn and Ni. Ca is able to inhibit the divalent metal transporter 1 (DMT1) in a dose-dependent manner to reduce Fe absorption and low Mg concentrations can exacerbate Fe deficiency. Pb competitively inhibits Fe distribution and elevated Cd absorption reduces Fe uptake. Exposure to Hg is associated with higher ferritin concentrations and Ni alters intracellular Fe metabolism. Fe removal by phlebotomy in hemochromatosis patients has shown to increase the levels of Cd and Pb and alter the concentrations of trace elements in some types of anemia. Yet, the effects of chronic exposure of most trace elements remain poorly understood.

  • Method Development for Omics Analyses using Schirmer Strips
    Morten Gundersen, Per Jensen, Christian Nilsen, Mazyar Yazdani, Øygunn Utheim, Elise Mørk Sandås, Helge Rootwelt, Kjell Gunnar Gundersen, and Katja Benedikte Prestø Elgstøen
    Informa UK Limited
    Abstract Purpose The aim of this article was to investigate whether Schirmer strips gathered during clinical dry eye examinations can be prepared for omics analyses in a standardized way, to adjust for variations in tear volume and enable two separate omics analyses from the same sample. In addition, the intention was to investigate whether fluorescein dye instillation in the eyes gave bias effects on metabolomic analysis. Methods Twelve samples from six individuals, with normal or reduced tear production, were collected. Half of the samples were harvested after instillation of fluorescein in the eye. Each strip was divided in half along the length and prepared with a new method for extracting tear content from the Schirmer strip. The new method was established to compensate for different dilutions of metabolites in varying Schirmer strip wetting levels when using identical extraction volume for all samples. Metabolomic data were compared in samples with and without fluorescein dye and Schirmer strips ranging from 1 to 35 mm wetting levels using a global LC–MS method. Results All samples were successfully analyzed with an average of ∼350 relevant features detected per sample after using both positive and negative electrospray ionization mode, despite low tear volumes in some samples and that only one half of the Schirmer strips were used. Principal component analysis plots and heatmaps revealed no bias effects of fluorescein dye presence or different Schirmer strip values when using the proposed method. Conclusion A high number of relevant metabolomic features can be extracted from longitudinally cut halves of Schirmer strips, which may enable analyses with more than one omics modality from the same sample. With the pre-analytical method described, Schirmer strips can be used for metabolomic analyses even in cases of very low or high tear volume with or without fluorescence.

  • Tear film lipid layer and corneal oxygenation: a new function?
    Mazyar Yazdani
    Springer Science and Business Media LLC

  • Bloodlettings in Hemochromatosis Result in Increased Blood Lead (Pb) Concentrations
    Mazyar Yazdani, Sonia Distante, Lars Mørkrid, Rune J. Ulvik, and Bjørn J. Bolann
    Springer Science and Business Media LLC
    AbstractHemochromatosis is a hereditary disorder, most often associated with mutations of the HFE (High FErrum) gene. If left untreated, it can result in severe parenchymal iron accumulation. Bloodletting is the mainstay treatment. We have previously shown that treatment of hemochromatosis by repeated bloodlettings may induce changes in the serum levels of several trace elements. The aim of this work was to evaluate if whole blood concentrations of the environmental pollutants lead (Pb), mercury (Hg), and cadmium (Cd) could be affected by bloodlettings. We recruited 28 patients and 21 healthy individuals (control group). Whole blood and urine levels of Pb, Hg, and Cd were measured before the start and after the completion of treatment using inductively coupled plasma mass spectrometry, together with serum iron and liver function tests. Concentrations of blood Pb, but not Hg or Cd, were significantly increased after treatment. The increase in Pb was higher in C282Y homozygous patients than in the other patients, and it was positively correlated with the serum concentration of alkaline phosphatase. Bloodlettings in hemochromatosis result in an increase in the blood concentration of Pb. Augmented absorption due to iron loss or Pb mobilization from bone may contribute to the higher blood Pb level.

  • Increased Sphingomyelin and Free Sialic Acid in Cerebrospinal Fluid of Kearns-Sayre Syndrome: New Findings Using Untargeted Metabolomics
    Cathrin Lytomt Salvador, Mari Oppebøen, Anja Østeby Vassli, Helle Cecilie Viekilde Pfeiffer, Kristin Nielsen Varhaug, Katja Benedikte Prestø Elgstøen, and Mazyar Yazdani
    Elsevier BV

  • Global Metabolomics Discovers Two Novel Biomarkers in Pyridoxine-Dependent Epilepsy Caused by ALDH7A1 Deficiency
    Hans-Otto Böhm, Mazyar Yazdani, Elise Mørk Sandås, Anja Østeby Vassli, Erle Kristensen, Helge Rootwelt, Hanne Bendiksen Skogvold, Eylert Brodtkorb, and Katja Benedikte Prestø Elgstøen
    MDPI AG
    Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive developmental and epileptic encephalopathy caused by pathogenic variants in the ALDH7A1 gene (PDE-ALDH7A1), which mainly has its onset in neonates and infants. Early diagnosis and treatment are crucial to prevent severe neurological sequelae or death. Sensitive, specific, and stable biomarkers for diagnostic evaluations and follow-up examinations are essential to optimize outcomes. However, most of the known biomarkers for PDE lack these criteria. Additionally, there is little discussion regarding the interdependence of biomarkers in the PDE-ALDH7A1 metabolite profile. Therefore, the aim of this study was to understand the underlying mechanisms in PDE-ALDH7A1 and to discover new biomarkers in the plasma of patients using global metabolomics. Plasma samples from 9 patients with genetically confirmed PDE-ALDH7A1 and 22 carefully selected control individuals were analyzed by ultra high performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS). Two novel and reliable pyridoxine-independent diagnostic markers, 6-hydroxy-2-aminocaproic acid (HACA) and an isomer of C9H11NO4, were identified. Furthermore, a possible reaction mechanism is proposed for HACA. This study demonstrates the capability of global metabolomics in disease screening to detect established and novel biomarkers.

  • The Therapeutic Benefits of Nanoencapsulation in Drug Delivery to the Anterior Segment of the Eye: A Systematic Review
    Madhavi Bhandari, Sanko Nguyen, Mazyar Yazdani, Tor Paaske Utheim, and Ellen Hagesaether
    Frontiers Media SA
    Background: Although numerous nanoparticle formulations have been developed for ocular administration, concerns are being raised about a possible mismatch between potential promises made by the field of nanoparticle research and demonstration of actual therapeutic benefit. Therefore, the primary focus of this present review was to critically assess to what extent nanoencapsulation of ocular drugs improved the therapeutic outcome when treating conditions in the anterior segment of the eye.Methods: A systematic search was conducted using Medline, PubMed, and Embase databases as well as Google Scholar for published peer-reviewed articles in English focusing on conventional nanoparticles used as drug delivery systems to the anterior segment of the eye in in vivo studies. The major therapeutic outcomes were intraocular pressure, tear secretion, number of polymorphonuclear leucocytes and pupil size. The outcome after encapsulation was compared to the non-encapsulated drug.Results: From the search, 250 results were retrieved. Thirty-eight studies met the inclusion criteria. Rabbits were used as study subjects in all but one study, and the number of animals ranged from 3 to 10. Coated and uncoated liposomes, lipid-based and polymeric nanoparticles, as well as micelles, were studied, varying in both particle size and surface charge, and encapsulating a total of 24 different drugs, including 6 salts. The majority of the in vivo studies demonstrated some improvement after nanoencapsulation, but the duration of the benefit varied from less than 1 h to more than 20 h. The most common in vitro methods performed in the studies were drug release, transcorneal permeation, and mucin interaction.Discussion: Nanoparticles that are small and mucoadhesive, often due to positive surface charge, appeared beneficial. Although in vitro assays can unravel more of the hidden and sophisticated interplay between the encapsulated drug and the nanoparticle structure, they suffered from a lack of in vitro—in vivo correlation. Therefore, more research should be focused towards developing predictive in vitro models, allowing rational design and systematic optimization of ocular nanoparticles with minimal animal experimentation.

  • A pioneer study on human 3-nitropropionic acid intoxication: Contributions from metabolomics
    Hanne Bendiksen Skogvold, Mazyar Yazdani, Elise Mørk Sandås, Anja Østeby Vassli, Erle Kristensen, Dagfinn Haarr, Helge Rootwelt, and Katja Benedikte Prestø Elgstøen
    Wiley
    AbstractThe neurotoxin 3‐nitropropionic acid (3‐NPA) is an inhibitor of succinate dehydrogenase, an enzyme participating both in the citric acid cycle and the mitochondrial respiratory chain. In human intoxications, it produces symptoms such as vomiting and stomach ache in mild cases, and dystonia, coma, and sometimes death in severe cases. We report the results from a liquid chromatography‐Orbitrap mass spectrometry metabolomics study mapping the metabolic impacts of 3‐NPA intoxication in plasma, urine, and cerebrospinal fluid (CSF) samples of a Norwegian boy initially suspected to suffer from a mitochondrial disease. In addition to the identification of 3‐NPA, our findings included a large number of annotated/identified altered metabolites (80, 160, and 62 in plasma, urine, and CSF samples, respectively) belonging to different compound classes, for example, amino acids, fatty acids, and purines and pyrimidines. Our findings indicated protective mechanisms to attenuate the toxic effects of 3‐NPA (e.g., decreased oleamide), occurrence of increased oxidative stress in the patient (such as increased free fatty acids and hypoxanthine) and energy turbulence caused by the intoxication (e.g., increased succinate). To our knowledge, this is the first case of 3‐NPA intoxication reported in Norway and the first published metabolomics study of human 3‐NPA intoxication worldwide. The unexpected identification of 3‐NPA illustrates the importance for health care providers to consider intake‐related intoxications during diagnostic evaluations, treatment and follow‐up examinations for neurotoxicity and a wide range of metabolic derangements.

  • Uncontrolled Oxygen Levels in Cultures of Retinal Pigment Epithelium: Have We Missed the Obvious?
    Mazyar Yazdani
    Informa UK Limited
    Abstract Retinal pigment epithelium (RPE) is the outermost layer of retina located between the photoreceptor cells and the choroid. This highly-polarized monolayer provides critical support for the functioning of the other parts of the retina, especially photoreceptors. Methods of culturing RPE have been under development since its establishment in 1920s. Despite considering various factors, oxygen (O2) levels in RPE microenvironments during culture preparation and experimental procedure have been overlooked. O2 is a crucial parameter in the cultures, and therefore, maintaining RPE cells at O2 levels different from their native environment (70–90 mm Hg of O2) could have unintended consequences. Owing to the importance of the topic, lack of sufficient discussion in the literature and to encourage future research, this paper will focus on uncontrolled O2 levels in cultures of RPE cells.

  • Eye Make-up Products and Dry Eye Disease: A Mini Review
    Mazyar Yazdani, Katja Benedikte Prestø Elgstøen, and Tor Paaske Utheim
    Informa UK Limited
    ABSTRACT Dry eye disease (DED), a multifactorial condition of the tear film and ocular surface, is one of the leading reasons for patients seeking eye care. Despite the multiple toxic ingredients of eye make-up products and their long-term application close to the ocular surface, few studies have analyzed their role in initiating and worsening DED. Females and the elderly experience the highest prevalence of DED and may be particularly vulnerable to the effects of eye make-up. The multifactorial nature of DED and common mechanisms behind several ocular surface diseases make it difficult to link a particular ingredient-driven mechanism to DED. Therefore, here, we list potential responses to eye cosmetics that may be involved in DED development. The first part of this review introduces the anatomy of the eye and DED, the second section explains the classification of eye cosmetic products, and the final part discusses the undesired effects under physical, pathogenic, and chemical insults.

  • Is oxidative stress an overlooked player in pyridoxine-dependent epilepsy? A focused review
    Mazyar Yazdani and Katja Benedikte Prestø Elgstøen
    Elsevier BV

  • Tear film break-up time and dry eye disease severity in a large norwegian cohort
    Mazyar Yazdani, Jørgen Fiskådal, Xiangjun Chen, Øygunn A. Utheim, Sten Ræder, Valeria Vitelli, and Tor P. Utheim
    MDPI AG
    This study evaluated to what extent tear film break-up time (TFBUT) could discriminate pathological scores for other clinical tests and explore the associations between them. Dry eye patients (n = 2094) were examined for ocular surface disease index (OSDI), tear film osmolarity (Osm), TFBUT, blink interval, ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test, meibomian expressibility, meibomian quality, and meibomian gland dysfunction. The results were grouped into eight levels of break-up time (≤2, ≥3, ≤5, ≥6, ≤10, ≥11, ≤15, and ≥16) with or without sex stratification. Receiver-operating characteristic curve (ROC) analysis and Pearson’s correlation coefficients were used to study TFBUT’s discriminative power and the associations among the tests, respectively. Above and below each TFBUT’s cut-off, all of the parameters indicated significant difference between groups, except OSDI (cut-off 15 s) and Osm (cut-offs 5 s–15 s). At TFBUT cut-off of 2 s, sex difference could be detected for OSDI, Osm, and OSS. OPI presented the strongest discriminative power and association with TFBUT in sharp contrast to Osm, holding the poorest discriminative power with no significant correlation. The remaining parameters were within the poor to very poor categories, both with regard to discrimination and correlation. In conclusion, patients with lower TFBUT presented with more severe DED parameters at all four defined cut-off values.

  • Response of human oral mucosal epithelial cells to different storage temperatures: A structural and transcriptional study
    Mazyar Yazdani, Aboulghassem Shahdadfar, Sjur Reppe, Dipak Sapkota, Evan M. Vallenari, Majlinda Lako, Che J. Connon, Francisco C. Figueiredo, and Tor Paaske Utheim
    Public Library of Science (PLoS)
    PurposeSeeking to improve the access to regenerative medicine, this study investigated the structural and transcriptional effects of storage temperature on human oral mucosal epithelial cells (OMECs).MethodsCells were stored at four different temperatures (4°C, 12°C, 24°C and 37°C) for two weeks. Then, the morphology, cell viability and differential gene expression were examined using light and scanning electron microscopy, trypan blue exclusion test and TaqMan gene expression array cards, respectively.ResultsCells stored at 4°C had the most similar morphology to non-stored controls with the highest viability rate (58%), whereas the 37°C group was most dissimilar with no living cells. The genes involved in stress-induced growth arrest (GADD45B) and cell proliferation inhibition (TGFB2) were upregulated at 12°C and 24°C. Upregulation was also observed in multifunctional genes responsible for morphology, growth, adhesion and motility such asEFEMP1(12°C) andEPHA4(4°C–24°C). Among genes used as differentiation markers,PPARAandTP53(along with its associated geneCDKN1A) were downregulated in all temperature conditions, whereasKRT1andKRT10were either unchanged (4°C) or downregulated (24°C and 12°C; and 24°C, respectively), except for upregulation at 12°C forKRT1.ConclusionsCells stored at 12°C and 24°C were stressed, although the expression levels of some adhesion-, growth- and apoptosis-related genes were favourable. Collectively, this study suggests that 4°C is the optimal storage temperature for maintenance of structure, viability and function of OMECs after two weeks.

  • Utility of Tear Osmolarity Measurement in Diagnosis of Dry Eye Disease
    Bezhod Tashbayev, Tor Paaske Utheim, Øygunn Aass Utheim, Sten Ræder, Janicke Liaaen Jensen, Mazyar Yazdani, Neil Lagali, Valeria Vitelli, Darlene A. Dartt, and Xiangjun Chen
    Springer Science and Business Media LLC
    AbstractThe prevalence of dry eye disease is high worldwide and poses a great burden on patients’ daily lives. Accurate diagnosis of the disease is important, and it requires application of various methods. Hyperosmolarity is believed to be the disease marker and thus measuring it provides useful information. In this study we investigated utility of tear osmolarity measured with TearLab osmometer, along with other diagnostic tests (Ocular Surface Disease Index questionnaire, Tear film break-up time, Ocular Protection Index, Ocular Surface Staining, Schirmer I test, Meibomian gland functionality in 757 patients (1514 eyes) with dry eye disease and 29 healthy controls (58 eyes). Statistical differences between the patient group and the control group were observed for all the tests apart from tear osmolarity, regardless of cut-off value (&gt;308 mOsm/L, &gt;316 mOsm/L, and inter-eye difference &gt;8 mOsm/L). Moreover, in the receiver operating characteristics curve analyses tear osmolarity measurement could not discriminate dry eye disease pathological scores. Therefore, our study suggests that tear osmolarity measured with TearLab osmometer cannot be used as a key indicator of DED.

  • Intense pulsed light treatment in meibomian gland dysfunction: A concise review
    Behzod Tashbayev, Mazyar Yazdani, Reiko Arita, Fredrik Fineide, and Tor Paaske Utheim
    Elsevier BV

  • Distinct Subsets of Noncoding RNAs Are Strongly Associated With BMD and Fracture, Studied in Weight-Bearing and Non–Weight-Bearing Human Bone
    Kaare M Gautvik, Clara-Cecilie Günther, Vid Prijatelj, Carolina Medina-Gomez, Enisa Shevroja, Leila Heidary Rad, Mazyar Yazdani, Einar Lindalen, Haldor Valland, Vigdis T Gautvik,et al.
    Oxford University Press (OUP)
    ABSTRACTWe investigated mechanisms resulting in low bone mineral density (BMD) and susceptibility to fracture by comparing noncoding RNAs (ncRNAs) in biopsies of non–weight-bearing (NWB) iliac (n = 84) and weight bearing (WB) femoral (n = 18) postmenopausal bone across BMDs varying from normal (T-score &amp;gt; −1.0) to osteoporotic (T-score ≤ −2.5). Global bone ncRNA concentrations were determined by PCR and microchip analyses. Association with BMD or fracture, adjusted by age and body mass index, were calculated using linear and logistic regression and least absolute shrinkage and selection operator (Lasso) analysis. At 10% false discovery rate (FDR), 75 iliac bone ncRNAs and 94 femoral bone ncRNAs were associated with total hip BMD. Eight of the ncRNAs were common for the two sites, but five of them (miR-484, miR-328-3p, miR-27a-5p, miR-28-3p, and miR-409-3p) correlated positively to BMD in femoral bone, but negatively in iliac bone. Of predicted pathways recognized in bone metabolism, ECM-receptor interaction and proteoglycans in cancer emerged at both sites, whereas fatty acid metabolism and focal adhesion were only identified in iliac bone. Lasso analysis and cross-validations identified sets of nine bone ncRNAs correlating strongly with adjusted total hip BMD in both femoral and iliac bone. Twenty-eight iliac ncRNAs were associated with risk of fracture (FDR &amp;lt; 0.1). The small nucleolar RNAs, RNU44 and RNU48, have a function in stabilization of ribosomal RNAs (rRNAs), and their association with fracture and BMD suggest that aberrant processing of rRNAs may be involved in development of osteoporosis. Cis-eQTL (expressed quantitative trait loci) analysis of the iliac bone biopsies identified two loci associated with microRNAs (miRNAs), one previously identified in a heel-BMD genomewide association study (GWAS). In this comprehensive investigation of the skeletal genetic background in postmenopausal women, we identified functional bone ncRNAs associated to fracture and BMD, representing distinct subsets in WB and NWB skeletal sites. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

  • Comparative toxicity of selected PAHs in rainbow trout hepatocytes: genotoxicity, oxidative stress and cytotoxicity
    Mazyar Yazdani
    Informa UK Limited
    Abstract Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in aquatic ecosystems, which may have potentially toxic effects on organisms. In this study occurrence of DNA strand breaks, oxidative stress, and cytotoxicity were investigated in rainbow trout hepatocytes following in vitro exposure for 24 h to four PAHs (0.01–10 µM): naphthalene, fluoranthene, pyrene, and benzo[a]pyrene (B[a]P). The exposed hepatocytes were analyzed for DNA strand breaks using the comet assay and for antioxidant status by measuring intracellular glutathione (GSH) content using the fluorescent probe mBCl. The cytotoxicity of PAHs was assessed using the fluorescent probe CFDA-AM. The results showed that fluoranthene, pyrene, and B[a]P were genotoxic at all exposure concentrations, whereas naphthalene was genotoxic at concentrations ≥0.1 µM. All treatments reduced the intracellular concentrations of GSH for all four PAHs, except 10 µM of B[a]P, suggesting that some level of oxidative stress was present. The cytotoxic effect was observed for naphthalene at concentrations ≥0.1 µM and pyrene at all exposure concentrations, whereas fluoranthene and B[a]P were not cytotoxic at the tested concentrations. The study shows that low-molecular-weight PAHs may cause DNA strand breaks as high-molecular-weight PAHs do in fish tissue. In addition, two- to five-ring PAHs can induce oxidative stress and cytotoxicity.

  • A hyaluronan hydrogel scaffold for culture of human oral mucosal epithelial cells in limbal stem-cell therapy
    Mazyar Yazdani, Aboulghassem Shahdadfar, Catherine Joan Jackson, and Tor Paaske Utheim
    MDPI AG
    Hyaluronan (HA), a major component of the extracellular matrix, plays a key role in cell proliferation, growth, survival, polarization and differentiation. We investigated the optimization of a HA hydrogel scaffold for culture of human oral mucosal epithelial cells (OMECs) for potential application in limbal stem cell therapy. The effect of the optimized scaffold on OMEC cell sheet morphology, cell metabolic activity and expression of genes associated with stemness, adherence and cell damage was studied. The results indicate that HA hydrogels crosslinked with polyethylene glycol diacrylate (PEGDA) failed to support OMEC attachment and growth. However, HA hydrogel scaffolds dried for three days and coated with 1 mg/mL collagen IV produced a full OMEC sheet. Cell morphology was comparable to control after three weeks culture, maintaining 76% metabolic activity. Of apoptosis-related genes, the pro-apoptotic markers CASP3 and BAX2 were upregulated and downregulated, respectively, compared to control whereas the anti-apoptotic marker BCL2 was downregulated. The expression level of stemness genes ΔNp63α and ABCG2 was significantly higher than control. Genes associated with improved scar-less wound healing (integrin-αV) and protection of the ocular surface (cadherin-1) had ~3-fold increased expression. These data suggest that our optimized HA-hydrogel scaffold could enhance culture of OMEC cell sheets for use in ocular reconstruction.

  • Evaluation of the Ocular Surface Disease Index Questionnaire as a Discriminative Test for Clinical Findings in Dry Eye Disease Patients
    Mazyar Yazdani, Xiangjun Chen, Behzod Tashbayev, Øygunn A. Utheim, Sten Ræder, Yanjun Hua, Jon R. Eidet, Aleksandar Stojanovic, Darlene A. Dartt, and Tor P. Utheim
    Informa UK Limited
    ABSTRACT Purpose To investigate to what extent the OSDI can be utilized as a discriminative test for clinical findings. Methods One thousand and ninety patients with dry eye disease (DED) were consecutively included and examined for osmolarity, tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), meibum quality (MQ), and diagnosis of meibomian gland dysfunction (MGD). Receiver-operating characteristic curve (ROC) analysis considering optimum balanced sensitivity and specificity (close to 50%) was used for assessment. Results The present study on more than 1,000 patients indicates that the OSDI in the ROC curve analysis is a poor discriminator of pathological scores for TFBUT ≤ 5 (AUC = 0.553; p = .012) and ≤10 s (AUC = 0.608; p = .002), OSS ≥ 3 (AUC = 0.54; p = .043), ST ≤ 5 (AUC = 0.550; p = .032) and ≤10 mm/5 min (AUC = 0.544; p = .016), and ME ≥ 1 (AUC = 0.594; p = <0.001). Pathological scores for osmolarity >308 and >316 mOsm/L, OPI, OSS > 1, MQ, and MGD could not be discriminated by OSDI (p > .05). Conclusion Cut-off values for the OSDI can be defined to discriminate pathological TFBUT (≤5 and ≤10), OSS (≥3), ST (≤5 and ≤10) and ME, however, the discriminability was low. Our comprehensive study emphasises the importance of taking both symptoms and signs into account in DED management.

  • Tear metabolomics in dry eye disease: A review
    Mazyar Yazdani, Katja Benedikte Prestø Elgstøen, Helge Rootwelt, Aboulghassem Shahdadfar, Øygunn Aass Utheim, and Tor Paaske Utheim
    MDPI AG
    Dry eye disease (DED) is a multifactorial syndrome that can be caused by alteration in the quality or quantity of the precorneal tear film. It is considered one of the most common ocular conditions leading patients to seek eye care. The current method for diagnostic evaluations and follow-up examinations of DED is a combination of clinical signs and symptoms determined by clinical tests and questionnaires, respectively. The application of powerful omics technologies has opened new avenues toward analysis of subjects in health and disease. Metabolomics is a new emerging and complementary research discipline to all modern omics in the comprehensive analysis of biological systems. The identification of distinct metabolites and integrated metabolic profiles in patients can potentially inform clinicians at an early stage or during monitoring of disease progression, enhancing diagnosis, prognosis, and the choice of therapy. In ophthalmology, metabolomics has gained considerable attention over the past decade but very limited such studies have been reported on DED. This paper aims to review the application of tear metabolomics in DED.

  • Hyaluronan-based hydrogel scaffolds for limbal stem cell transplantation: A review
    Mazyar Yazdani, Aboulghassem Shahdadfar, Catherine Joan Jackson, and Tor Paaske Utheim
    MDPI AG
    Hyaluronan (HA), also termed hyaluronic acid or hyaluronate, is a major component of the extracellular matrix. This non-sulfated glycosaminoglycan plays a key role in cell proliferation, growth, survival, polarization, and differentiation. The diverse biological roles of HA are linked to the combination of HA’s physicochemical properties and HA-binding proteins. These unique characteristics have encouraged the application of HA-based hydrogel scaffolds for stem cell-based therapy, a successful method in the treatment of limbal stem cell deficiency (LSCD). This condition occurs following direct damage to limbal stem cells and/or changes in the limbal stem cell niche microenvironment due to intrinsic and extrinsic insults. This paper reviews the physical properties, synthesis, and degradation of HA. In addition, the interaction of HA with other extracellular matrix (ECM) components and receptor proteins are discussed. Finally, studies employing HA-based hydrogel scaffolds in the treatment of LSCD are reviewed.

  • Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort
    Mazyar Yazdani, Xiangjun Chen, Behzod Tashbayev, Øygunn A. Utheim, Sten Ræder, Neil Lagli, Aleksandar Stojanovic, Darlene A. Dartt, and Tor P. Utheim
    Informa UK Limited
    ABSTRACT Purpose To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. Methods Patients (n = 1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15 mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p ≤ 0.05). Results The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). Conclusions Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited.

RECENT SCHOLAR PUBLICATIONS

  • Tear Global Metabolomic Differences in Pre-Operative Cataract Patients With and Without Dry Eye Disease
    M Gundersen, C Nilsen, P Jensen, M Yazdani, Utheim, ES Sand, ...
    Current Eye Research, 1-11 2025

  • Can endogenous ethylene glycol production occur in humans? A detailed investigation of adult monozygotic twin sisters (Sept, 10.1080/15563650.2024. 2401076, 2024)
    M Ghannoum, PJ Waters, KE Hovda, G Choquette, KBP Elgstoen, ...
    CLINICAL TOXICOLOGY 62 (11), 785-785 2024

  • Can endogenous ethylene glycol production occur in humans? A detailed investigation of adult monozygotic twin sisters
    M Ghannoum, PJ Waters, KE Hovda, G Choquette, KBP Elgsten, ...
    Clinical Toxicology 62 (11), 698-706 2024

  • Cellular and molecular responses to mitochondrial DNA deletions in Kearns-Sayre Syndrome: some underlying mechanisms
    M Yazdani
    Molecular Neurobiology 61 (8), 5665-5679 2024

  • Iron metabolism, calcium, magnesium and trace elements: a review
    T Rolić, M Yazdani, S Mandić, S Distante
    Biological Trace Element Research, 1-10 2024

  • Method Development for Omics Analyses using Schirmer Strips
    M Gundersen, P Jensen, C Nilsen, M Yazdani, Utheim, EM Sands, ...
    Current Eye Research 49 (7), 708-716 2024

  • Tear film lipid layer and corneal oxygenation: a new function?
    M Yazdani
    Eye 37 (17), 3534-3541 2023

  • A transcriptomic study of native, expanded, and engineered human corneal endothelial cells (Retraction of Vol 102, Pg E 139, 2024)
    A Shahdadfar, M Yazdani
    ACTA OPHTHALMOLOGICA 2023

  • Bloodlettings in hemochromatosis result in increased blood lead (Pb) concentrations
    M Yazdani, S Distante, L Mrkrid, RJ Ulvik, BJ Bolann
    Biological Trace Element Research 201 (7), 3193-3201 2023

  • Increased sphingomyelin and free sialic acid in cerebrospinal fluid of Kearns-Sayre syndrome: new findings using untargeted metabolomics
    CL Salvador, M Oppeben, A Vassli, HCV Pfeiffer, KN Varhaug, ...
    Pediatric Neurology 143, 68-76 2023

  • Global metabolomics discovers two novel biomarkers in pyridoxine-dependent epilepsy caused by ALDH7A1 deficiency
    HO Bhm, M Yazdani, EM Sands, A steby Vassli, E Kristensen, ...
    International Journal of Molecular Sciences 23 (24), 16061 2022

  • Evaluation of the Ocular Surface Disease Index Questionnaire as a Discriminative Test for Clinical Findings in Dry Eye Disease Patients (vol 44, pg 941, 2019)
    M Yazdani, X Chen, B Tashbayev, OA Utheim, S Raeder, Y Hua, JR Eidet, ...
    CURRENT EYE RESEARCH 47 (9), II 2022

  • The therapeutic benefits of nanoencapsulation in drug delivery to the anterior segment of the eye: a systematic review
    M Bhandari, S Nguyen, M Yazdani, TP Utheim, E Hagesaether
    Frontiers in Pharmacology 13, 903519 2022

  • Uncontrolled oxygen levels in cultures of retinal pigment epithelium: have we missed the obvious?
    M Yazdani
    Current Eye Research 47 (5), 651-660 2022

  • A pioneer study on human 3‐nitropropionic acid intoxication: Contributions from metabolomics
    H Bendiksen Skogvold, M Yazdani, EM Sands, A steby Vassli, ...
    Journal of Applied Toxicology 42 (5), 818-829 2022

  • Eye make-up products and dry eye disease: a mini review
    M Yazdani, KBP Elgsten, TP Utheim
    Current Eye Research 47 (1), 1-11 2022

  • Is Oxidative Stress an Overlooked Player in Pyridoxine-dependent Epilepsy? A Focused Review
    M Yazdani, KBP Elgsten
    Seizure 2021

  • Tear film break-up time and dry eye disease severity in a large Norwegian cohort
    M Yazdani, J Fiskdal, X Chen, A Utheim, S Rder, V Vitelli, TP Utheim
    Journal of Clinical Medicine 10 (4), 884 2021

  • Response of human oral mucosal epithelial cells to different storage temperatures: A structural and transcriptional study
    M Yazdani, A Shahdadfar, S Reppe, D Sapkota, EM Vallenari, M Lako, ...
    Plos one 15 (12), e0243914 2020

  • Distinct subsets of noncoding RNAs are strongly associated with BMD and fracture, studied in weight‐bearing and non–weight‐bearing human bone
    KM Gautvik, CC Gnther, V Prijatelj, C Medina‐Gomez, E Shevroja, ...
    Journal of Bone and Mineral Research 35 (6), 1065-1076 2020

MOST CITED SCHOLAR PUBLICATIONS

  • Concerns in the application of fluorescent probes DCDHF-DA, DHR 123 and DHE to measure reactive oxygen species in vitro
    M Yazdani
    Toxicology in Vitro 30, 578-582 2015
    Citations: 99

  • Intense pulsed light treatment in meibomian gland dysfunction: a concise review
    B Tashbayev, M Yazdani, R Arita, F Fineide, TP Utheim
    The ocular surface 18 (4), 583-594 2020
    Citations: 93

  • Tear Metabolomics in Dry Eye Disease: A Review
    M Yazdani, KBP Elgsten, H Rootwelt, A Shahdadfar, A Utheim, ...
    International Journal of Molecular Sciences 20 (15), 3755 2019
    Citations: 89

  • Effects of metal-contaminated soils on the accumulation of heavy metals in different parts of Centella asiatica: a laboratory study
    CK Yap, MR Mohd Fitri, M Yazdani, SG Tan
    Sains Malaysiana 39 (3), 347-352 2010
    Citations: 73

  • Prenatal exposure to bisphenol A interferes with the development of cerebellar granule neurons in mice and chicken
    GH Mathisen, M Yazdani, KE Rakkestad, PK Aden, J Bodin, M Samuelsen, ...
    International Journal of Developmental Neuroscience 31 (8), 762-769 2013
    Citations: 67

  • An in vitro study on the adsorption, absorption and uptake capacity of Zn by the bioremediator Trichoderma atroviride
    M Yazdani, CK Yap, F Abdullah, SG Tan
    Environment Asia 3 (1), 53-59 2010
    Citations: 61

  • Hyaluronan-Based Hydrogel Scaffolds for Limbal Stem Cell Transplantation: A Review
    M Yazdani, A Shahdadfar, CJ Jackson, TP Utheim
    Cells 8 (3), 245 2019
    Citations: 51

  • Utility of tear osmolarity measurement in diagnosis of dry eye disease
    B Tashbayev, TP Utheim, A Utheim, S Rder, JL Jensen, M Yazdani, ...
    Scientific Reports 10 (1), 5542 2020
    Citations: 50

  • Species-dependent sensitivity to contaminants: An approach using primary hepatocyte cultures with three marine fish species
    KS Ellesat, M Yazdani, TF Holth, K Hylland
    Marine environmental research 72 (4), 216-224 2011
    Citations: 40

  • Comparative toxicity of selected PAHs in rainbow trout hepatocytes: genotoxicity, oxidative stress and cytotoxicity
    M Yazdani
    Drug and chemical toxicology, 1-8 2018
    Citations: 38

  • Short-term effect of bisphenol-a on oxidative stress responses in Atlantic salmon kidney cell line: a transcriptional study
    M Yazdani, AMS Andresen, T Gjen
    Toxicology Mechanisms and Methods 26 (4), 295-300 2016
    Citations: 34

  • Trichoderma atroviride as a bioremediator of Cu pollution: An in vitro study
    M Yazdani, CK Yap, F Abdullah, SG Tan
    Toxicological and Environ Chemistry 91 (7), 1305-1314 2009
    Citations: 33

  • Technical aspects of oxygen level regulation in primary cell cultures: A review
    M Yazdani
    Interdisciplinary toxicology 9 (3–4), 85–89 2016
    Citations: 30

  • A pioneer study on human 3‐nitropropionic acid intoxication: Contributions from metabolomics
    H Bendiksen Skogvold, M Yazdani, EM Sands, A steby Vassli, ...
    Journal of Applied Toxicology 42 (5), 818-829 2022
    Citations: 29

  • Eye make-up products and dry eye disease: a mini review
    M Yazdani, KBP Elgsten, TP Utheim
    Current Eye Research 47 (1), 1-11 2022
    Citations: 26

  • Fibrous shape underlies the mutagenic and carcinogenic potential of nanosilver while surface chemistry affects the biosafety of iron oxide nanoparticles
    A Gbelov, N El Yamani, TI Alonso, B Buliakov, A Srančkov, ...
    Mutagenesis 32 (1), 193-202 2017
    Citations: 26

  • Tear film break-up time and dry eye disease severity in a large Norwegian cohort
    M Yazdani, J Fiskdal, X Chen, A Utheim, S Rder, V Vitelli, TP Utheim
    Journal of Clinical Medicine 10 (4), 884 2021
    Citations: 23

  • Evaluation of the Ocular Surface Disease Index Questionnaire as a Discriminative Test for Clinical Findings in Dry Eye Disease Patients
    M Yazdani, X Chen, B Tashbayev, A Utheim, S Rder, Y Hua, JR Eidet, ...
    Current eye research 2019
    Citations: 16

  • Distinct subsets of noncoding RNAs are strongly associated with BMD and fracture, studied in weight‐bearing and non–weight‐bearing human bone
    KM Gautvik, CC Gnther, V Prijatelj, C Medina‐Gomez, E Shevroja, ...
    Journal of Bone and Mineral Research 35 (6), 1065-1076 2020
    Citations: 14

  • Is Oxidative Stress an Overlooked Player in Pyridoxine-dependent Epilepsy? A Focused Review
    M Yazdani, KBP Elgsten
    Seizure 2021
    Citations: 13