AKUImg: A database of cartilage images of Alkaptonuria patients

Rossi, Alberto; Giacomini, Giorgia; Cicaloni, Vittoria; Galderisi, Silvia; Milella, Maria Serena; Bernini, Andrea; Millucci, Lia; Spiga, Ottavia; Bianchini, Monica; Santucci, Annalisa

doi:10.1016/j.compbiomed.2020.103863

Cited by 10 publications

(7 citation statements)

References 26 publications

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“…Furthermore, our results might support the use of SAA as a clinically relevant disease activity and severity marker in AKU. Overall, the datasets generated here along with those already stored in our AKU database [ 66 , 67 , 68 ] could be amenable to further analyses through artificial intelligence tools [ 66 , 67 , 68 , 69 , 70 , 71 ], helping us to better understand AKU and the analysis of genotype-phenotype correlations, possibly leading to a precision-medicine approach to AKU.…”

Section: Discussionmentioning

confidence: 99%

Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies

Braconi

Geminiani²,

Psarelli³

et al. 2022

Cells

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Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis.

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Section: Discussionmentioning

confidence: 99%

Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies

Braconi

Geminiani²,

Psarelli³

et al. 2022

Cells

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“…12). These new findings and information will be integrated in ApreciseKUre, an AKUdedicated digital platform where all the biochemical, genetic clinical information, images and data regarding AKU pathophysiology are collected and analyzed with the aim to promote a better understanding of molecular mechanisms and signaling pathways in AKU and in other related co-morbidities [60][61][62][63][64][65].…”

Section: Discussionmentioning

confidence: 99%

Homogentisic acid induces autophagy alterations leading to chondroptosis in human chondrocytes: Implications in Alkaptonuria

Galderisi

Milella

Rossi

et al. 2022

Archives of Biochemistry and Biophysics

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“…This follows the idea of personalizing the treatment according to “personal” and pathological characteristics and is justified by the fact that in AKU, similarly to most rare genetic conditions, current state-of-the-art treatment is inadequate. The only drug that is currently approved for the treatment of AKU, nitisinone, can decrease urinary excretion of HGA and slow down the progression of the disease, but it comes with unwanted side effects and uncertainty on the most suitable timing to start treatment [ 106 ]; An unsupervised clustering method able to stratify AKU population into subgroups with similar features to obtain a first genotype/phenotype stratification of AKU subjects and investigate the distribution of HGD mutations across the obtained clusters [ 133 ]; A plugin named AKUImg, the first AKU-dedicated image repository, created for the storage and analysis of AKU histopathological slides [ 134 ]. By providing clinicians and researchers with a tool that can differentiate between AKU and healthy cartilage slides, it might help the scientific community to screen slides for an extremely rare condition such as AKU.…”

Section: A Digital Platform For Aku: Aprecisekurementioning

confidence: 99%

“…A plugin named AKUImg, the first AKU-dedicated image repository, created for the storage and analysis of AKU histopathological slides [ 134 ]. By providing clinicians and researchers with a tool that can differentiate between AKU and healthy cartilage slides, it might help the scientific community to screen slides for an extremely rare condition such as AKU.…”

Section: A Digital Platform For Aku: Aprecisekurementioning

confidence: 99%

Alkaptonuria: From Molecular Insights to a Dedicated Digital Platform

Milella,

Geminiani,

Trezza

et al. 2024

Cells

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Alkaptonuria (AKU) is a genetic disorder that affects connective tissues of several body compartments causing cartilage degeneration, tendon calcification, heart problems, and an invalidating, early-onset form of osteoarthritis. The molecular mechanisms underlying AKU involve homogentisic acid (HGA) accumulation in cells and tissues. HGA is highly reactive, able to modify several macromolecules, and activates different pathways, mostly involved in the onset and propagation of oxidative stress and inflammation, with consequences spreading from the microscopic to the macroscopic level leading to irreversible damage. Gaining a deeper understanding of AKU molecular mechanisms may provide novel possible therapeutical approaches to counteract disease progression. In this review, we first describe inflammation and oxidative stress in AKU and discuss similarities with other more common disorders. Then, we focus on HGA reactivity and AKU molecular mechanisms. We finally describe a multi-purpose digital platform, named ApreciseKUre, created to facilitate data collection, integration, and analysis of AKU-related data.

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AKUImg: A database of cartilage images of Alkaptonuria patients

Cited by 10 publications

References 26 publications

Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies

Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies

Homogentisic acid induces autophagy alterations leading to chondroptosis in human chondrocytes: Implications in Alkaptonuria

Alkaptonuria: From Molecular Insights to a Dedicated Digital Platform

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