Article
Pediatrics
Yunguo Zhou, Yucai Liu, Yang Shen, Fang Xu, Fei Xu, Hui Huang, Junkai Duan
Summary: The clinical characteristics and disease outcomes of a pedigree with compound heterozygous mutations in the SLC22A5 gene were investigated. Serum acylcarnitine profiles were analyzed using tandem mass spectrometry, and high-throughput sequencing was performed on DNA samples from patients and their first-degree relatives. The study found that both patients carried compound heterozygous mutations in the SLC22A5 gene, inherited from their mother and father, respectively. Early L-carnitine supplementation significantly improved or resolved clinical symptoms. The study suggests that compound mutations in SLC22A5 can lead to different clinical manifestations, especially at different ages.
FRONTIERS IN PEDIATRICS
(2023)
Article
Biochemistry & Molecular Biology
Anna Papierniak-Wygladala, Weronika Lamch, Ewelina Jurewicz, Katarzyna A. Nalecz
Summary: L-carnitine plays a crucial role in the transfer of fatty acids to mitochondria for beta-oxidation, which has gained attention in cancer research. The majority of carnitine in humans comes from the diet and enters the cell through solute carriers, mainly the organic cation/carnitine transporter OCTN2/SLC22A5. Studies on breast epithelial cell lines showed that OCTN2 is present as a non-glycosylated form and is regulated by the protein SEC24C, which is phosphorylated by the kinase AKT. Inhibition of AKT decreased the level of mature OCTN2 and affected carnitine transport. This highlights the potential of AKT and OCTN2 as targets for combination therapy in breast cancer.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Pharmacology & Pharmacy
Dongfeng Sun, Qingfa Chen, Zhibo Gai, Fengxia Zhang, Xiaoqing Yang, Wensi Hu, Chengyu Chen, Guangjie Yang, Severin Hoermann, Gerd. A. Kullak-Ublick, Michele Visentin
Summary: Esophageal cancer is the ninth most common malignancy worldwide, and platinum derivatives' cytotoxic activity largely depends on organic cation transporters (OCTs) uptake and accumulation. Higher OCTN2 expression in tumor tissues of esophageal cancer patients treated with oxaliplatin correlated with reduced risk of recurrence and longer survival time.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Katerina Novakova, Michael Toeroek, Miljenko Panajatovic, Jamal Bouitbir, Francois H. T. Duong, Christoph Handschin, Stephan Kraehenbuehl
Summary: The transcription of the SLC22A5 gene is regulated by PPAR-alpha and MEF2 transcription factors. PGC-1 alpha and the p38 MAPK signaling cascade also play a role in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Lieke M. M. van den Heuvel, Adriana Kater-Kuipers, Tessa van Dijk, Loek L. L. Crefcoeur, Gepke Visser, Mirjam Langeveld, Lidewij Henneman
Summary: This study explored the experiences and opinions of women diagnosed with primary carnitine deficiency through newborn bloodspot screening. The findings showed that these women did not experience major psychological distress following the diagnosis, but the lack of information caused feelings of uncertainty and anxiety. They believed that screening for primary carnitine deficiency is beneficial for newborns and also for their own health.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Environmental Sciences
Xiaofang Wang, Lingyu Hu, Caiyun Wang, Bingnan He, Zhengwei Fu, Cuiyuan Jin, Yuanxiang Jin
Summary: A recent study found that pregnant women had high levels of IMZ due to dietary exposure. In a mouse experiment, exposure to IMZ during gestation and lactation periods resulted in significant changes in growth phenotypes, carnitine levels, and gut microbiota in the offspring. Maternal IMZ exposure also affected carnitine absorption and disrupted gut microbiota balance.
Article
Medicine, Research & Experimental
Yohan Bignon, Leonore Wigger, Camille Ansermet, Benjamin D. Weger, Sylviane Lagarrigue, Gabriel Centeno, Fanny Durussel, Lou Gotz, Mark Ibberson, Sylvain Pradervand, Manfredo Quadroni, Meltem Weger, Francesca Amati, Frederic Gachon, Dmitri Firsov
Summary: Rhythmic adaptations in renal metabolism are suggested by circadian rhythmicity in renal function. By studying diurnal changes in renal metabolic pathways, we found that a significant number of RNAs, proteins, and metabolites in the kidneys of control mice display rhythmicity. Disruptions in key metabolic pathways were observed in the kidneys of mice with an inducible deletion of the circadian clock regulator Bmal1, resulting in impaired mitochondrial activity. The reabsorption of carnitine from primary urine was particularly affected, leading to decreased plasma and tissue carnitine levels.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Genetics & Heredity
Duo Zhou, Yi Cheng, Xiaoshan Yin, Haixia Miao, Zhenzhen Hu, Jianbin Yang, Yu Zhang, Benqing Wu, Xinwen Huang
Summary: The aim of this study was to investigate the incidence, biochemical characteristics, and genetic traits of disorders of mitochondrial carnitine-acylcarnitine cycle in newborn screening (NBS) in Zhejiang province, China. A total of 20 patients with these disorders were identified among 4,070,375 newborns screened by tandem mass spectrometry. The overall incidence was low, and most patients exhibited typical acylcarnitine profiles. Patients with CPT2D/CACTD had a higher mortality rate. Several novel mutations in CPT1A and CPT2 genes were identified, broadening the spectrum of variants.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Barbara Juraszek, Joanna Czarnecka-Herok, Katarzyna A. Nalecz
Summary: Research indicates that glioma cell survival heavily relies on fatty acid oxidation (FAO) and SLC22A5 activity, suggesting that CPT1 and SLC22A5 may be potential drug targets.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Negar Dinarvand, Farzaneh Karimi, Reza Azizi, Sedighe Rastaghi, Abdolkarim Sheikhi, Morteza Pourfarzam
Summary: This study aims to evaluate the expression of OCTN2 and its association with clinicopathological characteristics in breast cancer. The findings reveal that OCTN2 expression is significantly higher in breast cancer tissues compared to adjacent normal tissues. It is positively correlated with tumor size and Ki-67, and negatively correlated with the progesterone receptor (PR) status. OCTN2 expression may serve as a prognostic biomarker and a tumor oncogene, and a potential therapeutic target.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Medicine, General & Internal
Michael Jakoby, Amruta Jaju, Aundrea Marsh, Andrew Wilber
Summary: Primary carnitine deficiency is a rare genetic disorder caused by mutations in the SLC22A5 gene, leading to reduced carnitine transport and subsequent effects on fatty acid oxidation and carnitine excretion. In some cases, maternal metabolic genetic disorders can be identified through newborn screening, and maternal carnitine levels should be monitored after a positive newborn screen for PCD.
JOURNAL OF INVESTIGATIVE MEDICINE HIGH IMPACT CASE REPORTS
(2021)
Article
Physiology
Benjamin T. Wall, David Machin, Mandy V. Dunlop, Francis B. Stephens
Summary: Increasing skeletal muscle carnitine content can manipulate fuel metabolism and improve exercise performance. Intravenous insulin infusion during hypercarnitinemia increases plasma carnitine clearance and Na+-dependent muscle carnitine accretion, likely via stimulating Na+/K+ ATPase pump activity. Ingestion of high-dose caffeine stimulates plasma carnitine clearance during hypercarnitinemia, likely via increased Na+/K+ ATPase activity. Carnitine co-ingestion with caffeine may represent a novel muscle carnitine loading strategy in humans, and therefore manipulate skeletal muscle fuel metabolism and improve exercise performance.
PHYSIOLOGICAL REPORTS
(2023)
Review
Nutrition & Dietetics
Hiroyuki Takashima, Takashi Maruyama, Masanori Abe
Summary: Carnitine is a naturally occurring amino acid derivative involved in the transport of long-chain fatty acids and energy production. In patients on dialysis, serum carnitine levels may decrease due to restricted dietary intake and deprivation of endogenous synthesis, leading to various clinical disorders. Levocarnitine administration may help replenish free carnitine and increase carnitine levels in muscle, potentially improving symptoms in dialysis patients.
Article
Genetics & Heredity
Xiangchun Yang, Qiong Li, Fei Wang, Lulu Yan, Danyan Zhuang, Haiyan Qiu, Haibo Li, Liang Chen
Summary: This study identified the prevalence of PCD in Ningbo city through newborn screening and expanded the variant spectrum of SLC22A5. The findings demonstrate the clinical value of combining NBS program results with DNA analysis for the diagnosis of PCD.
FRONTIERS IN GENETICS
(2021)
Article
Medical Laboratory Technology
Weihua Lin, Kunyi Wang, Zhenzhu Zheng, Yanru Chen, Caifeng Fu, Yiming Lin, Dongmei Chen
Summary: The incidence of primary carnitine deficiency (PCD) is relatively high in the Quanzhou area. Newborn screening is effective in early detection of PCD, and the identification of new SLC22A5 gene mutations broadens the mutation spectrum. Timely supplementation of L-carnitine can help prevent sudden death in PCD patients.
CLINICA CHIMICA ACTA
(2021)
Article
Genetics & Heredity
Nicola Longo, Orly Ardon, Rena Vanzo, Elizabeth Schwartz, Marzia Pasquali
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2011)
Article
Biochemistry & Molecular Biology
Uzochi Chimdinma Ndukwe Erlingsson, Francesco Iacobazzi, Aiping Liu, Orly Ardon, Marzia Pasquali, Nicola Longo
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2013)
Article
Microbiology
Blaine A. Mathison, Jessica L. Kohan, John F. Walker, Richard Boyd Smith, Orly Ardon, Marc Roger Couturier
JOURNAL OF CLINICAL MICROBIOLOGY
(2020)
Article
Medical Laboratory Technology
Orly Ardon, Robert L. Schmidt
LABORATORY MEDICINE
(2020)
Review
Pathology
Matthew G. Hanna, Victor E. Reuter, Orly Ardon, David Kim, Sahussapont Joseph Sirintrapun, Peter J. Schuffler, Klaus J. Busam, Jennifer L. Sauter, Edi Brogi, Lee K. Tan, Bin Xu, Tejus Bale, Narasimhan P. Agaram, Laura H. Tang, Lora H. Ellenson, John Philip, Lorraine Corsale, Evangelos Stamelos, Maria A. Friedlander, Peter Ntiamoah, Marc Labasin, Christine England, David S. Klimstra, Meera Hameed
Article
Medical Laboratory Technology
Peter J. Schueffler, Evangelos Stamelos, Ishtiaque Ahmed, Vijay K. Yarlagadda, Orly Ardon, Matthew G. Hanna, Victor E. Reuter, David S. Klimstra, Meera Hameed
Summary: This study aims to define and quantify relevant performance metrics for efficient visualization of cases and slides in digital slide viewers. The study results show that performance metrics such as time to open a case, time to change a slide, and time to change a field of view contribute to improving the configuration of the viewer, leading to increased efficiency for pathologists in routine digital pathology.
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2022)
Correction
Pathology
Matthew G. Hanna, Orly Ardon, Victor E. Reuter, Sahussapont Joseph Sirintrapun, Christine England, David S. Klimstra, Meera R. Hameed
Review
Pathology
Matthew G. Hanna, Orly Ardon, Victor E. Reuter, Christine England, David S. Klimstra, Meera R. Hameed
Summary: Anatomic pathology has seen significant advancements in technology in the past few decades, with digital pathology systems integrating into clinical practice to provide new opportunities in the medical field.
Correction
Pathology
Matthew G. Hanna, Orly Ardon, Victor E. Reuter, Christine England, David S. Klimstra, Meera R. Hameed
Review
Oncology
Matthew G. G. Hanna, Orly Ardon
Summary: Pathology laboratories are utilizing digital pathology systems to enhance patient care. These systems allow pathologists to perform tasks digitally rather than using traditional glass slides and microscopes. The integration of image analysis and machine learning enables computer assisted diagnostics and has the potential to greatly improve pathology practices and patient care.
GENES CHROMOSOMES & CANCER
(2023)
Article
Medicine, Research & Experimental
Orly Ardon, Marc Labasin, Maria Friedlander, Allyne Manzo, Lorraine Corsale, Peter Ntiamoah, Jeninne Wright, Kojo Elenitoba-Johnson, Victor E. Reuter, Meera R. Hameed, Matthew G. Hanna
Summary: Digital pathology workflows can enhance pathology operations by improving image retrieval, reviewing slides digitally, enabling remote work and telepathology, utilizing computer-aided tools, and sharing images for research and education. This article presents the development of a structured quality management system (QMS) specifically tailored for clinical digital pathology operations at Memorial Sloan Kettering Cancer Center. The article also provides recommendations for implementing a QMS in large-scale digital pathology operations.
LABORATORY INVESTIGATION
(2023)
Article
Computer Science, Information Systems
Peter J. Schueffler, Luke Geneslaw, D. Vijay K. Yarlagadda, Matthew G. Hanna, Jennifer Samboy, Evangelos Stamelos, Chad Vanderbilt, John Philip, Marc-Henri Jean, Lorraine Corsale, Allyne Manzo, Neeraj H. G. Paramasivam, John S. Ziegler, Jianjiong Gao, Juan C. Perin, Young Suk Kim, Umeshkumar K. Bhanot, Michael H. A. Roehrl, Orly Ardon, Sarah Chiang, Dilip D. Giri, Carlie S. Sigel, Lee K. Tan, Melissa Murray, Christina Virgo, Christine England, Yukako Yagi, S. Joseph Sirintrapun, David Klimstra, Meera Hameed, Victor E. Reuter, Thomas J. Fuchs
Summary: The study introduced a comprehensive digital pathology solution in a large academic medical center, including a viewer for clinical workflows, research applications, and educational processes, as well as an interconnected tool for compiling and sharing research datasets. The implementation of these solutions led to increased adoption of digital pathology and facilitated next-generation computational pathology for enhanced cancer research.
JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
(2021)
Article
Genetics & Heredity
O. Ardon, M. Procter, R. Mao, N. Longo, Y. E. Landau, A. Shilon-Hadass, L. V. Gabis, C. Hoffmann, M. Tzadok, G. Heimer, S. Sada, B. Ben-Zeev, Y. Anikster
MOLECULAR GENETICS AND METABOLISM REPORTS
(2016)
Article
Genetics & Heredity
O. Ardon, M. Procter, T. Tvrdik, N. Longo, R. Mao
MOLECULAR GENETICS AND METABOLISM REPORTS
(2014)