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1

دورية أكاديمية

Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes.

المؤلفون: Nomoto, Hiroshi, Pei, Lina, Montemurro, Chiara, Rosenberger, Madeline, Furterer, Allison, Coppola, Giovanni, Nadel, Brian, Pellegrini, Matteo, Gurlo, Tatyana, Butler, Peter C, Tudzarova, Slavica

المصدر: Diabetologia. 63(1)

الوصف: Aims/hypothesisThe conserved hypoxia inducible factor 1 α (HIF1α) injury-response pro-survival pathway has recently been implicated in early beta cell dysfunction but slow beta cell loss in type 2 diabetes. We hypothesised that the unexplained prolonged prediabetes phase in type 1 diabetes may also be, in part, due to activation of the HIF1α signalling pathway.MethodsRNA sequencing (RNA-Seq) data from human islets with type 1 diabetes or after cytokine exposure in vitro was evaluated for activation of HIF1α targets. This was corroborated by immunostaining human pancreases from individuals with type 1 diabetes for 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), the key effector of HIF1α-mediated metabolic remodelling, and by western blotting of islets and INS-1 832/13 cells exposed to cytokines implicated in type 1 diabetes.ResultsHIF1α signalling is activated (p = 4.5 × 10-9) in islets from individuals with type 1 diabetes, and in human islets exposed in vitro to cytokines implicated in type 1 diabetes (p = 1.1 × 10-14). Expression of PFKFB3 is increased fivefold (p

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2

Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy

المؤلفون: Strandberg, Kristin, Ayoglu, Burcu, Roos, A., Reza, M., Niks, E., Signorelli, M., Fasterius, Erik, 1987, Pontén, F., Lochmüller, H., Domingos, J., Ala, P., Muntoni, F., Aartsma-Rus, A., Spitali, P., Nilsson, Peter, Al-Khalili Szigyarto, Cristina

المصدر: Journal of Neuromuscular Diseases. 7(3):231-246

مصطلحات موضوعية: Affinity-based proteomics, disease progression, Duchenne muscular dystrophy, protein biomarkers, serum and plasma, carbonate dehydratase III, collagen type 1, dystrophin, electron transferring flavoprotein, electron transferring flavoprotein A, lactate dehydrogenase, lactate dehydrogenase B, malate dehydrogenase, malate dehydrogenase 2, microtubule associated protein 4, myosin light chain, myosin light chain 3, nestin, troponin T, unclassified drug, adolescent, adult, aged, Article, blood sampling, breathing, child, controlled study, correlation analysis, disease course, female, gene mutation, human, immunohistochemistry, longitudinal study, major clinical study, male, middle aged, mobilization, preschool child, priority journal, protein analysis, protein expression, protein microarray, school child, six minute walk test, Western blotting, young adult

الوصف: Background: Duchenne Muscular Dystrophy is a severe, incurable disorder caused by mutations in the dystrophin gene. The disease is characterized by decreased muscle function, impaired muscle regeneration and increased inflammation. In a clinical context, muscle deterioration, is evaluated using physical tests and analysis of muscle biopsies, which fail to accurately monitor the disease progression. Objectives: This study aims to confirm and asses the value of blood protein biomarkers as disease progression markers using one of the largest longitudinal collection of samples. Methods: A total of 560 samples, both serum and plasma, collected at three clinical sites are analyzed using a suspension bead array platform to assess 118 proteins targeted by 250 antibodies in microliter amount of samples. Results: Nine proteins are confirmed as disease progression biomarkers in both plasma and serum. Abundance of these biomarkers decreases as the disease progresses but follows different trajectories. While carbonic anhydrase 3, microtubule associated protein 4 and collagen type I alpha 1 chain decline rather constantly over time, myosin light chain 3, electron transfer flavoprotein A, troponin T, malate dehydrogenase 2, lactate dehydrogenase B and nestin plateaus in early teens. Electron transfer flavoprotein A, correlates with the outcome of 6-minutes-walking-test whereas malate dehydrogenase 2 together with myosin light chain 3, carbonic anhydrase 3 and nestin correlate with respiratory capacity. Conclusions: Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-284778Test
https://doi.org/10.3233/JND-190454Test

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3

دورية أكاديمية

Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti-PD-1 Therapies in Metastatic Melanoma.

المصدر: Clinical cancer research : an official journal of the American Association for Cancer Research. 24(21)

الوصف: Purpose: PD-1/L1 axis-directed therapies produce clinical responses in a subset of patients; therefore, biomarkers of response are needed. We hypothesized that quantifying key immunosuppression mechanisms within the tumor microenvironment by multiparameter algorithms would identify strong predictors of anti-PD-1 response.Experimental Design: Pretreatment tumor biopsies from 166 patients treated with anti-PD-1 across 10 academic cancer centers were fluorescently stained with multiple markers in discovery (n = 24) and validation (n = 142) cohorts. Biomarker-positive cells and their colocalization were spatially profiled in pathologist-selected tumor regions using novel Automated Quantitative Analysis algorithms. Selected biomarker signatures, PD-1/PD-L1 interaction score, and IDO-1/HLA-DR coexpression were evaluated for anti-PD-1 treatment outcomes.Results: In the discovery cohort, PD-1/PD-L1 interaction score and/or IDO-1/HLA-DR coexpression was strongly associated with anti-PD-1 response (P = 0.0005). In contrast, individual biomarkers (PD-1, PD-L1, IDO-1, HLA-DR) were not associated with response or survival. This finding was replicated in an independent validation cohort: patients with high PD-1/PD-L1 and/or IDO-1/HLA-DR were more likely to respond (P = 0.0096). These patients also experienced significantly improved progression-free survival (HR = 0.36; P = 0.0004) and overall survival (HR = 0.39; P = 0.0011). In the combined cohort, 80% of patients exhibiting higher levels of PD-1/PD-L1 interaction scores and IDO-1/HLA-DR responded to PD-1 blockers (P = 0.000004). In contrast, PD-L1 expression was not predictive of survival.Conclusions: Quantitative spatial profiling of key tumor-immune suppression pathways by novel digital pathology algorithms could help more reliably select melanoma patients for PD-1 monotherapy. Clin Cancer Res; 24(21); 5250-60. ©2018 AACR.

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الوصول الحر: https://escholarship.org/uc/item/92k1g956Test

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4

دورية أكاديمية

Clinical genomic profiling identifies TYK2 mutation and overexpression in patients with neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors.

المؤلفون: Hirbe, Angela C, Kaushal, Madhurima, Sharma, Mukesh Kumar, Dahiya, Sonika, Pekmezci, Melike, Perry, Arie, Gutmann, David H

المصدر: Cancer. 123(7)

الوصف: BackgroundMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that arise at an estimated frequency of 8% to 13% in individuals with neurofibromatosis type 1 (NF1). Compared with their sporadic counterparts, NF1-associated MPNSTs (NF1-MPNSTs) develop in young adults, frequently recur (approximately 50% of cases), and carry a dismal prognosis. As such, most individuals affected with NF1-MPNSTs die within 5 years of diagnosis, despite surgical resection combined with radiotherapy and chemotherapy.MethodsClinical genomic profiling was performed using 1000 ng of DNA from 7 cases of NF1-MPNST, and bioinformatic analyses were conducted to identify genes with actionable mutations.ResultsA total of 3 women and 4 men with NF1-MPNST were identified (median age, 38 years). Nonsynonymous mutations were discovered in 4 genes (neurofibromatosis type 1 [NF1], ROS proto-oncogene 1 [ROS1], tumor protein p53 [TP53], and tyrosine kinase 2 [TYK2]), which in addition were mutated in other MPNST cases in this sample set. Consistent with their occurrence in individuals with NF1, all tumors had at least 1 mutation in the NF1 gene. Whereas TP53 gene mutations are frequently observed in other cancers, ROS1 mutations are common in melanoma (15%-35%), another neural crest-derived malignancy. In contrast, TYK2 mutations are uncommon in other malignancies (

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الوصول الحر: https://escholarship.org/uc/item/8vp640shTest

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5

دورية أكاديمية

Alterations in cancer stem-cell marker CD44 expression predict oncologic outcome in soft-tissue sarcomas.

المؤلفون: Henderson, Timothy, Chen, Mingyi, Darrow, Morgan A, Li, Chin-Shang, Chiu, Chi-Lu, Monjazeb, Arta M, Murphy, William J, Canter, Robert J

الوصف: BackgroundCancer stem cells (CSCs) have been shown to resist chemotherapy and promote metastasis after cytotoxic therapies. We sought to determine if the expression of CSC markers (aldehyde dehydrogenase [ALDH], CD44, and epidermal growth factor receptor [EGFR]) predicted outcomes in soft-tissue sarcoma (STS) patients.MethodsWe queried an institutional database of 23 STS patients and evaluated immunohistochemical expression of CSC markers ALDH, CD44, and EGFR. The Cancer Genome Atlas (TCGA) was also queried for STS clinical and genomic data. Disease-specific (DSS) and overall survival (OS) were assessed by univariate and Kaplan-Meier analysis.ResultsOf the 23 institutional patients, the majority was female, had high-grade tumors and had extremity tumors. With a median follow-up of 27 months, nine patients (39%) experienced distant recurrence, and four (17%) died of disease. Mean H-scores at diagnosis (±standard error of the mean) for CD44, ALDH1, and EGFR were 169 ± 27, 77 ± 15, and 144 ± 23, respectively. On univariate analysis, there was a trend for increased CD44 score to predict both worse DSS and OS (hazard ratio = 1.01, 95% confidence interval 1-1.02, P = 0.056), whereas ALDH and EGFR scores did not. Analysis of 74 TCGA STS cases with complete clinical and genomic data revealed that CD44 copy number alterations predicted worse DSS (9.89 months versus 72.5 months, P = 0.007) and a trend for worse OS (14.03 months versus 38.6 months, P = 0.12), whereas ALDH1 and EGFR copy number alteration did not. Multivariate analysis of the combined data sets was consistent with worse DSS among patients with higher CD44 expression.ConclusionsInstitutional and national TCGA data show the association of elevated baseline CD44 expression with worse STS outcomes. Further study of CD44 as a possible novel STS biomarker appears indicated.

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الوصول الحر: https://escholarship.org/uc/item/0716629nTest

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6

دورية أكاديمية

Programmed Death-Ligand 1 Expression and Response to the Anti–Programmed Death 1 Antibody Pembrolizumab in Melanoma

المصدر: Journal of Clinical Oncology. 34(34)

الوصف: Purpose Expression of programmed death-ligand 1 (PD-L1) is a potential predictive marker for response and outcome after treatment with anti-programmed death 1 (PD-1). This study explored the relationship between anti-PD-1 activity and PD-L1 expression in patients with advanced melanoma who were treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Six hundred fifty-five patients received pembrolizumab10 mg/kg once every 2 weeks or once every 3 weeks, or 2 mg/kg once every 3 weeks. Tumor response was assessed every 12 weeks per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent central review. Primary outcome was objective response rate. Secondary outcomes included progression-free survival (PFS) and overall survival (OS). Membranous PD-L1 expression in tumor and tumor-associated immune cells was assessed by a clinical trial immunohistochemistry assay (22C3 antibody) and scored on a unique melanoma (MEL) scale of 0 to 5 by one of three pathologists who were blinded to clinical outcome; a score ≥ 2 (membranous staining in ≥ 1% of cells) was considered positive. Results Of 451 patients with evaluable PD-L1 expression, 344 (76%) had PD-L1-positive tumors. Demographic and staging variables were equally distributed among PD-L1-positive and -negative patients. An association between higher MEL score and higher response rate and longer PFS (hazard ratio, 0.76; 95% CI, 0.71 to 0.82) and OS (hazard ratio, 0.76; 95% CI, 0.69 to 0.83) was observed ( P < .001 for each). Objective response rate was 8%, 12%, 22%, 43%, 57%, and 53% for MEL 0, 1, 2, 3, 4, and 5, respectively. Conclusion PD-L1 expression in pretreatment tumor biopsy samples was correlated with response rate, PFS, and OS; however, patients with PD-L1-negative tumors may also achieve durable responses.

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7

دورية أكاديمية

A murine model of inflammation-induced cerebral microbleeds

المؤلفون: Sumbria, Rachita K, Grigoryan, Mher Mahoney, Vasilevko, Vitaly, Krasieva, Tatiana B, Scadeng, Miriam, Dvornikova, Alexandra K, Paganini-Hill, Annlia, Kim, Ronald, Cribbs, David H, Fisher, Mark J

المصدر: Journal of Neuroinflammation. 13(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Neurosciences, Immunology, Brain Disorders, Neurodegenerative, Hematology, Sepsis, 2.1 Biological and endogenous factors, Aetiology, Neurological, Animals, Blood-Brain Barrier, Brain, Cerebral Hemorrhage, Disease Models, Animal, Female, Inflammation, Lipopolysaccharides, Male, Mice, Mice, Inbred C57BL, Microvessels, Animal models, Cerebral microhemorrhage, Cerebral microbleeds, Hemosiderin, adaptor protein, glial fibrillary acidic protein, immunoglobulin G, intercellular adhesion molecule 1, protein Iba1, unclassified drug, lipopolysaccharide, adult, animal experiment, animal model, animal tissue, Article, blood brain barrier, brain cortex, brain hemorrhage, cell activation, controlled study, female, fluorescence microscopy, immunohistochemistry, inflammation, male, mouse, nervous system inflammation, nonhuman, nuclear magnetic resonance imaging, subcortex, animal, brain, C57BL mouse, chemically induced, diagnostic imaging, disease model, drug effects, metabolism, microvasculature, Clinical Sciences, Neurology & Neurosurgery

الوصف: BackgroundCerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to study cerebral microbleeds.MethodsAdult C57BL/6 mice were injected with LPS (3 or 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. At 2 or 7 days after the first injection, brains were harvested. Hematoxylin and eosin (H&E) and Prussian blue (PB) were used to stain fresh (acute) hemorrhages and hemosiderin (sub-acute) hemorrhages, respectively. Brain tissue ICAM-1, IgG, Iba1, and GFAP immunohistochemistry were used to examine endothelium activation, blood-brain barrier (BBB) disruption, and neuroinflammation. MRI and fluorescence microscopy were used to further confirm CMH development in this model.ResultsLPS-treated mice developed H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. No surface and negligible H&E-positive CMH were observed in saline-treated mice (n = 12). LPS (3 mg/kg; n = 10) produced significantly higher number, size, and area of H&E-positive CMH at 2 days. LPS (1 mg/kg; n = 9) produced robust development of PB-positive CMH at 7 days, with significantly higher number and area compared with saline (n = 9)-treated mice. CMH showed the highest distribution in the cerebellum followed by the sub-cortex and cortex. LPS-induced CMH were predominantly adjacent to cerebral capillaries, and CMH load was associated with indices of brain endothelium activation, BBB disruption, and neuroinflammation. Fluorescence microscopy confirmed the extravasation of red blood cells into the brain parenchyma, and MRI demonstrated the presence of cerebral microbleeds.ConclusionsLPS produced rapid and robust development of H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. The ease of development of both H&E- and PB-positive CMH makes the LPS-induced mouse model suitable to study inflammation-induced CMH.

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8

دورية أكاديمية

N-3 PUFA Deficiency Affects the Ultrastructural Organization and Density of White Matter Microglia in the Developing Brain of Male Mice ; Front Cell Neurosci.

المؤلفون: DECOEUR, Fanny, PICARD, Katherine, ST‐PIERRE, Marie‐Kim, GREENHALGH, Andrew D., DELPECH, Jean-Christophe, SERE, Alexandra, LAYE, Sophie, TREMBLAY, Marie-Eve, NADJAR, Agnes

الوصف: Over the last century, westernization of dietary habits has led to a dramatic reduction in dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs). In particular, low maternal intake of n-3 PUFAs throughout gestation and lactation causes defects in brain myelination. Microglia are recognized for their critical contribution to neurodevelopmental processes, such as myelination. These cells invade the white matter in the first weeks of the post-natal period, where they participate in oligodendrocyte maturation and myelin production. Therefore, we investigated whether an alteration of white matter microglia accompanies the myelination deficits observed in the brain of n-3 PUFA-deficient animals. Macroscopic imaging analysis shows that maternal n-3 PUFA deficiency decreases the density of white matter microglia around post-natal day 10. Microscopic electron microscopy analyses also revealed alterations of microglial ultrastructure, a decrease in the number of contacts between microglia and myelin sheet, and a decreased amount of myelin debris in their cell body. White matter microglia further displayed increased mitochondrial abundance and network area under perinatal n-3 PUFA deficiency. Overall, our data suggest that maternal n-3 PUFA deficiency alters the structure and function of microglial cells located in the white matter of pups early in life, and this could be the key to understand myelination deficits during neurodevelopment. Copyright © 2022 Decoeur, Picard, St-Pierre, Greenhalgh, Delpech, Sere, Layé, Tremblay and Nadjar. ; Développment d'une infrastructure française distribuée coordonnée ; University of Bordeaux Neurocampus Graduate School

العلاقة: https://oskar-bordeaux.fr/handle/20.500.12278/170232Test

الإتاحة: https://doi.org/20.500.12278/170232Test
https://doi.org/10.3389/fncel.2022.802411Test
https://oskar-bordeaux.fr/handle/20.500.12278/170232Test
https://hdl.handle.net/20.500.12278/170232Test

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9

دورية أكاديمية

HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition

المؤلفون: Kis, Olena, Sankaran-Walters, Sumathi, Hoque, M Tozammel, Walmsley, Sharon L, Dandekar, Satya, Bendayan, Reina

المصدر: Antimicrobial Agents and Chemotherapy. 60(5)

مصطلحات موضوعية: Medical Microbiology, Biomedical and Clinical Sciences, Clinical Research, HIV/AIDS, Infectious Diseases, Prevention, Evaluation of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Aetiology, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1, ATP Binding Cassette Transporter, Subfamily G, Member 2, Adult, Anti-HIV Agents, Cytochrome P-450 CYP3A, Female, HIV Infections, HIV-1, Humans, Immunohistochemistry, Male, Middle Aged, Multidrug Resistance-Associated Protein 2, Multidrug Resistance-Associated Proteins, Real-Time Polymerase Chain Reaction, Transcriptome, Microbiology, Pharmacology and Pharmaceutical Sciences, Medical microbiology, Pharmacology and pharmaceutical sciences

الوصف: This study investigated the effects of HIV-1 infection and antiretroviral therapy (ART) on the expression of intestinal drug efflux transporters, i.e., P-glycoprotein (Pgp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP), and metabolic enzymes, such as cytochrome P450s (CYPs), in the human upper intestinal tract. Intestinal biopsy specimens were obtained from HIV-negative healthy volunteers, ART-naive HIV-positive (HIV(+)) subjects, and HIV(+) subjects receiving ART (10 in each group). Intestinal tissue expression of drug transporters and metabolic enzymes was examined by microarray, real-time quantitative reverse transcription-PCR (qPCR), and immunohistochemistry analyses. Microarray analysis demonstrated significantly lower expression of CYP3A4 and ABCC2/MRP2 in the HIV(+) ART-naive group than in uninfected subjects. qPCR analysis confirmed significantly lower expression of ABCC2/MRP2 in ART-naive subjects than in the control group, while CYP3A4 and ABCG2/BCRP showed a trend toward decreased expression. Protein expression of MRP2 and BCRP was also significantly lower in the HIV(+) naive group than in the control group and was partially restored to baseline levels in HIV(+) subjects receiving ART. In contrast, gene and protein expression of ABCB1/Pgp was significantly increased in HIV(+) subjects on ART relative to HIV(+) ART-naive subjects. These data demonstrate that the expression of drug-metabolizing enzymes and efflux transporters is significantly altered in therapy-naive HIV(+) subjects and in those receiving ART. Since CYP3A4, Pgp, MRPs, and BCRP metabolize or transport many antiretroviral drugs, their altered expression with HIV infection may negatively impact drug pharmacokinetics in HIV(+) subjects. This has clinical implications when using data from healthy volunteers to guide ART.

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الوصول الحر: https://escholarship.org/uc/item/55c9k27wTest

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10

دورية أكاديمية

Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto's Thyroiditis.

المؤلفون: Hepp, Michael, Wérion, Alexis, De Greef, Axel, de Ville de Goyet, Christine, de Bournonville, Marc, Behets Wydemans, Catherine, Lengele, Benoit, Daumerie, Chantal, Mourad, Michel, Ludgate, Marian, Many, Marie-Christine, Joris, Virginie, Craps, Julie

المساهمون: UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, Thyroid Research Group, Division of Infection & Immunity, Cardiff University School of Medicine - Heath Park, Cardiff CF14 4XN, UK, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique

المصدر: International journal of molecular sciences, Vol. 22, no.8 (2021)

الوصف: In Hashimoto's thyroiditis (HT), oxidative stress (OS) is driven by Th1 cytokines' response interfering with the normal function of thyrocytes. OS results from an imbalance between an excessive production of reactive oxygen species (ROS) and a lowering of antioxidant production. Moreover, OS has been shown to inhibit Sirtuin 1 (SIRT1), which is able to prevent hypoxia-inducible factor (HIF)-1α stabilization. The aims of this study were to determine the involvement of NADPH-oxidases (NOX), SIRT1, and HIF-1α in HT pathophysiology as well as the status of antioxidant proteins such as peroxiredoxin 1 (PRDX1), catalase, and superoxide dismutase 1 (SOD1). The protein expressions of NOX2, NOX4, antioxidant enzymes, SIRT1, and HIF-1α, as well as glucose transporter-1 (GLUT-1) and vascular endothelial growth factor A (VEGF-A), were analyzed by Western blot in primary cultures of human thyrocytes that were or were not incubated with Th1 cytokines. The same proteins were also analyzed by immunohistochemistry in thyroid samples from control and HT patients. In human thyrocytes incubated with Th1 cytokines, NOX4 expression was increased whereas antioxidants, such as PRDX1, catalase, and SOD1, were reduced. Th1 cytokines also induced a significant decrease of SIRT1 protein expression associated with an upregulation of HIF-1α, GLUT-1, and VEGF-A proteins. With the exception of PRDX1 and SOD1, similar results were obtained in HT thyroids. OS due to an increase of ROS produced by NOX4 and a loss of antioxidant defenses (PRDX1, catalase, SOD1) correlates to a reduction of SIRT1 and an upregulation of HIF 1α, GLUT-1, and VEGF-A. Our study placed SIRT1 as a key regulator of OS and we, therefore, believe it could be considered as a potential therapeutic target in HT.

العلاقة: boreal:248138; http://hdl.handle.net/2078Test.1/248138; info:pmid/33916948; urn:EISSN:1422-0067

الإتاحة: https://doi.org/10.3390/ijms22083806Test
http://hdl.handle.net/2078Test.1/248138

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