keyword
https://read.qxmd.com/read/37827586/biphosphoglycerate-mutase-a-novel-therapeutic-target-for-malaria
#21
JOURNAL ARTICLE
Alessia Azzuolo, Yunxiang Yang, Albert Berghuis, Nassima Fodil, Philippe Gros
Biphosphoglycerate mutase (BPGM) is a tri-functional enzyme expressed exclusively in erythroid cells and tissues that is responsible for the production of 2,3-biphosphoglycerate (2,3-BPG) through the Rapoport-Luebering shunt. The 2,3-BPG is required for efficient glycolysis and ATP production under anaerobic conditions, but is also a critical allosteric regulator of hemoglobin (Hb), acting to regulate oxygen release in peripheral tissues. In humans, BPGM deficiency is very rare, and is associated with reduced levels of erythrocytic 2,3-BPG and ATP, left shifted Hb-O2 dissociation curve, low P50, elevated Hb and constitutive erythrocytosis...
July 2023: Transfusion Medicine Reviews
https://read.qxmd.com/read/37797713/pyruvate-kinase-is-post-translationally-regulated-by-sirtuin-2-in-aedes-aegypti-mosquitoes
#22
JOURNAL ARTICLE
Natthida Petchampai, Jun Isoe, Prashanth Balaraman, Max Oscherwitz, Brendan H Carter, Cecilia G Sánchez, Patricia Y Scaraffia
We previously demonstrated that Aedes aegypti pyruvate kinase (AaPK) plays a key role in the regulation of both carbon and nitrogen metabolism in mosquitoes. To further elucidate whether AaPK can be post-translationally regulated by Ae. aegypti sirtuin 2 (AaSirt2), an NAD+ -dependent deacetylase that catalyzes the removal of acetyl groups from acetylated lysine residues, we conducted a series of analysis in non-starved and starved female mosquitoes. Transcriptional and protein profiles of AaSirt2, analyzed by qPCR and western blots, indicated that the AaSirt2 is differentially modulated in response to sugar or blood feeding in mosquito tissues dissected at different times during the first gonotrophic cycle...
October 3, 2023: Insect Biochemistry and Molecular Biology
https://read.qxmd.com/read/37792629/metabolomic-analysis-of-drosophila-melanogaster-larvae-lacking-pyruvate-kinase
#23
JOURNAL ARTICLE
Yasaman Heidarian, Jason P Tourigny, Tess D Fasteen, Nader H Mahmoudzadeh, Alexander J Hurlburt, Travis Nemkov, Julie A Reisz, Angelo D'Alessandro, Jason M Tennessen
Pyruvate kinase (Pyk) is a rate-limiting enzyme that catalyzes the final metabolic reaction in glycolysis. The importance of this enzyme, however, extends far beyond ATP production, as Pyk is also known to regulate tissue growth, cell proliferation, and development. Studies of this enzyme in Drosophila melanogaster are complicated by the fact that the fly genome encodes six Pyk paralogs whose functions remain poorly defined. To address this issue, we used sequence distance and phylogenetic approaches to demonstrate that the gene Pyk encodes the enzyme most similar to the mammalian Pyk orthologs, while the other five Drosophila Pyk paralogs have significantly diverged from the canonical enzyme...
October 4, 2023: G3: Genes—Genomes—Genetics
https://read.qxmd.com/read/37790365/deficiency-of-metabolic-regulator-pkm2-activates-the-pentose-phosphate-pathway-and-generates-tcf1-progenitor-cd8-t-cells-to-improve-checkpoint-blockade
#24
Geoffrey J Markowitz, Yi Ban, Diamile A Tavarez, Liron Yoffe, Enrique Podaza, Yongfeng He, Mitchell T Martin, Michael J P Crowley, Tito A Sandoval, Dingcheng Gao, M Laura Martin, Olivier Elemento, Juan R Cubillos-Ruiz, Timothy E McGraw, Nasser K Altorki, Vivek Mittal
TCF1 high progenitor CD8+ T cells mediate the efficacy of PD-1 blockade, however the mechanisms that govern their generation and maintenance are poorly understood. Here, we show that targeting glycolysis through deletion of pyruvate kinase muscle 2 (PKM2) results in elevated pentose phosphate pathway (PPP) activity, leading to enrichment of a TCF1 high central memory-like phenotype and increased responsiveness to PD-1 blockade in vivo . PKM2 KO CD8+ T cells showed reduced glycolytic flux, accumulation of glycolytic intermediates and PPP metabolites, and increased PPP cycling as determined by 1,2 13 C glucose carbon tracing...
September 21, 2023: Research Square
https://read.qxmd.com/read/37774070/validation-of-faecal-pyruvate-kinase-isoenzyme-type-m2-faecal-m2pk-quick-test-in-detection-of-colorectal-adenoma-and-adenocarcinoma-among-high-risk-malaysian-population
#25
JOURNAL ARTICLE
Mohd Azri Mohd Suan, Ying Zhuang Ng, Gerald Fitjerald Henry, Rosaida Md Said, Sattian Kollanthavelu, Muhammad Ikhwan Mustapha, Chee Hoong Hoe, Choon Kin Lee, Puthashanan Rajamanickam, Ibtisam Ismail, Huan-Keat Chan, Muhammad Radzi Abu Hassan
BACKGROUND: Colorectal neoplasia is a multistep process that can lead to the development of colorectal cancer. Colonoscopy is the gold standard for diagnosis and screening of colorectal cancer, but its uptake is often hindered by unpleasant experiences and logistic obstacles. Therefore, non-invasive biomarker tests such as the M2-pyruvate kinase (M2PK) test have been explored as a potential screening tool. OBJECTIVE: This study aims to evaluate the efficacy of the M2PK Quick Stool Test (ScheBo®) in detecting colorectal adenoma and adenocarcinoma in high-risk Malaysian populations using colonoscopy as the comparison...
September 1, 2023: Asian Pacific Journal of Cancer Prevention: APJCP
https://read.qxmd.com/read/37760001/red-blood-cells-from-individuals-with-lesch-nyhan-syndrome-multi-omics-insights-into-a-novel-s162n-mutation-causing-hypoxanthine-guanine-phosphoribosyltransferase-deficiency
#26
JOURNAL ARTICLE
Julie A Reisz, Monika Dzieciatkowska, Daniel Stephenson, Fabia Gamboni, D Holmes Morton, Angelo D'Alessandro
Lesch-Nyhan syndrome (LN) is an is an X-linked recessive inborn error of metabolism that arises from a deficiency of purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). The disease manifests severely, causing intellectual deficits and other neural abnormalities, hypercoagulability, uncontrolled self-injury, and gout. While allopurinol is used to alleviate gout, other symptoms are less understood, impeding treatment. Herein, we present a high-throughput multi-omics analysis of red blood cells (RBCs) from three pediatric siblings carrying a novel S162N HPRT1 mutation...
August 31, 2023: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/37752768/endothelial-cell-derived-lactate-triggers-bone-mesenchymal-stem-cell-histone-lactylation-to-attenuate-osteoporosis
#27
JOURNAL ARTICLE
Jinhui Wu, Miao Hu, Heng Jiang, Jun Ma, Chong Xie, Zheng Zhang, Xin Zhou, Jianquan Zhao, Zhengbo Tao, Yichen Meng, Zhuyun Cai, Tengfei Song, Chenglin Zhang, Rui Gao, Chang Cai, Hongyuan Song, Yang Gao, Tao Lin, Ce Wang, Xuhui Zhou
Blood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism in these processes remains unclear. The present study finds that ovariectomized mice exhibit reduced blood vessel density in the bone and reduced expression of the endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Endothelial cell (EC)-specific deletion of Pkm2 impairs osteogenesis and worsens osteoporosis in mice. This is attributed to the impaired ability of bone mesenchymal stem cells (BMSCs) to differentiate into osteoblasts...
September 26, 2023: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/37731369/bone-mineral-density-in-adult-patients-with-pyruvate-kinase-deficiency-on-long-term-mitapivat-treatment
#28
JOURNAL ARTICLE
Hanny Al-Samkari, Rachael F Grace, Andreas Glenthøj, Oliver Andres, Wilma Barcellini, Frédéric Galacteros, Kevin H M Kuo, D Mark Layton, Marta Morado, Vip Viprakasit, Feng Tai, Rolandas Urbstonaitis, Jaime Morales, Bryan McGee, Eduard J van Beers
Not available.
September 21, 2023: Haematologica
https://read.qxmd.com/read/37713687/mitapivat-a-quinolone-sulfonamide-to-manage-hemolytic-anemia-in-adults-with-pyruvate-kinase-deficiency
#29
JOURNAL ARTICLE
Josef Wills, Melissa Horenstein, Alicia Kim, Matthew A Silva, Lorena Dima
BACKGROUND: Pyruvate kinase (PK) deficiency is a rare enzyme-linked glycolytic defect resulting in mild-to-severe chronic persistent erythrocyte hemolysis. The disease is an autosomal recessive trait caused by mutations in the PK liver and red blood cell gene characterized by insufficient erythrocyte PK activity. PK deficiency is most diagnosed in persons of northern European descent and managed with packed red blood cell transfusions, chelation, and splenectomy with cholecystectomy. Mitapivat is the first approved therapy indicated for hemolytic anemia in adults with PK deficiency with the potential for delaying splenectomy in mild-moderate disease...
September 2023: American Journal of Therapeutics
https://read.qxmd.com/read/37688507/effects-of-2-3-dpg-knockout-on-scd-phenotype-in-townes-scd-model-mice
#30
JOURNAL ARTICLE
Amey Barakat, Reema Jasuja, Lindsay Tomlinson, Zane Wenzel, Lila Ramaiah, Betty A Petterson, Brendon Kapinos, Anagha Sawant, Vicente Pagan, Nathanael Lintner, Denise Field, Youngwook Ahn, Kelly M Knee
Sickle cell disease (SCD) is a severe, multisystemic hematological disorder that impacts nearly every major organ in adults. The current approved treatments for SCD directly target mutant hemoglobin or address downstream disease pathology. Several compounds targeting reduction of 2,3-DPG by activation of Pyruvate Kinase-R are currently being evaluated in SCD patients. In this study, we genetically engineered a mouse lacking 2,3-DPG on the Townes SCD mouse model background and evaluated the effects of 2,3-DPG loss on disease pathology...
September 9, 2023: American Journal of Hematology
https://read.qxmd.com/read/37674879/acute-on-chronic-liver-failure-and-successful-liver-transplantation-in-pyruvate-kinase-deficiency
#31
Baila Elkin, Daniela S Allende, Shreya Sengupta
Liver transplant is a rare phenomenon for pyruvate kinase deficiency (PKD)-related liver disease and can be mediated by multiple mechanisms. In this report, we present a 55-year-old man with PKD who had acute-on-chronic liver failure with kidney failure and marked hyperbilirubinemia. His liver disease was from recurrent cholangitis, cholestasis from hemolysis, and iron deposition (likely from both repeated transfusions in youth and chronic hemolysis), all consequences of his PKD. He received a liver transplant and had a good outcome...
September 2023: ACG Case Reports Journal
https://read.qxmd.com/read/37671043/case-report-a-rare-case-of-pyruvate-kinase-deficiency-and-crigler-najjar-syndrome-type-ii-with-a-novel-pathogenic-variant-of-pklr-and-ugt1a1-mutation
#32
Huan Wu, Long Wu, Quan Zhang, Bao-Fang Zhang
Pyruvate Kinase Deficiency (PKD) and Crigler-Najjar syndrome are rare autosomal recessive liver diseases. PKD is caused by homozygous or compound heterozygous mutations in the PKLR gene, leading to non-spherocytic hereditary hemolytic anemia. On the other hand, Crigler-Najjar syndrome (CNS-II) is characterized by the loss or reduced activity of UDP-glucuronosyltransferase, resulting in elevated levels of unconjugated bilirubin, which is the primary cause of disease manifestation. To date, there have been no reported cases of patients with both conditions...
2023: Frontiers in Genetics
https://read.qxmd.com/read/37647690/molecular-insights-of-a-cbp-%C3%AE-catenin-signaling-inhibitor-on-nonalcoholic-steatohepatitis-induced-liver-fibrosis-and-disorder
#33
JOURNAL ARTICLE
Kenzaburo Yamaji, Sadahiro Iwabuchi, Yuko Tokunaga, Shinichi Hashimoto, Daisuke Yamane, Sakiko Toyama, Risa Kono, Bouchra Kitab, Kyoko Tsukishima-Kohara, Yosuke Osawa, Yukiko Hayashi, Tsunekazu Hishima, Chise Tateno, Kiminori Kimura, Takeshi Okanoue, Michinori Kohara
Nonalcoholic steatohepatitis (NASH) is a progressive fibrotic disease associated with an increased risk of developing hepatocellular carcinoma; at present, no efficient therapeutic strategy has been established. Herein, we examined the efficacy of PRI-724, a potent inhibitor of CBP/β-catenin signaling, for treating NASH-related liver fibrosis and disorder and characterized its mechanism. Choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-fed mice exhibited NASH-induced liver fibrosis that is characterized by steatosis, lobular inflammation, hepatocellular injury and collagen fibrils...
August 28, 2023: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/37635967/clk2-in-gabaergic-neurons-is-critical-in-regulating-energy-balance-and-anxiety-like-behavior-in-a-gender-specific-fashion
#34
JOURNAL ARTICLE
Sónia Norberto, Heloisa Balan Assalin, Dioze Guadagnini, Natália Tobar, Patrícia Aline Boer, Min-Cheol Kang, Mario Jose Abdalla Saad, Young-Bum Kim, Patricia Oliveira Prada
INTRODUCTION: Cdc2-like kinase (CLK2) is a member of CLK kinases expressed in hypothalamic neurons and is activated in response to refeeding, leptin, or insulin. Diet-induced obesity and leptin receptor-deficient db/db mice lack CLK2 signal in the hypothalamic neurons. The neurotransmiter gamma-aminobutyric acid (GABA) is among the most prevalent in the central nervous system (CNS), particularly in the hypothalamus. Given the abundance of GABA-expressing neurons and their potential influence on regulating energy and behavioral homeostasis, we aimed to explore whether the deletion of CLK2 in GABAergic neurons alters energy homeostasis and behavioral and cognitive functions in both genders of mice lacking CLK2 in Vgat-expressing neurons (Vgat-Cre; Clk2loxP/loxP ) on chow diet...
2023: Frontiers in Endocrinology
https://read.qxmd.com/read/37627327/oxidative-stress-in-healthy-and-pathological-red-blood-cells
#35
REVIEW
Florencia Orrico, Sandrine Laurance, Ana C Lopez, Sophie D Lefevre, Leonor Thomson, Matias N Möller, Mariano A Ostuni
Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a significant role in the pathophysiology of red cell diseases...
August 18, 2023: Biomolecules
https://read.qxmd.com/read/37596712/an-innovative-phase-i-study-in-healthy-subjects-to-determine-the-mass-balance-elimination-metabolism-and-absolute-bioavailability-of-mitapivat
#36
JOURNAL ARTICLE
Chandra Prakash, Heidi Mangus, Yan Yan, Hua Yang, Varsha Iyer
Mitapivat, a first-in-class, oral, small-molecule, allosteric activator of the red blood cell-specific form of pyruvate kinase (PKR), was approved for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. In this phase I mass balance study in healthy males, we administered a single ~120 mg oral dose of [14 C]mitapivat and a concomitant intravenous ~0.1 mg microdose of [13 C6 ]mitapivat. We determined (1) the routes of total radioactivity excretion, including the mass balance of total radioactivity in urine and feces; (2) the pharmacokinetics of mitapivat and [13 C6 ]mitapivat in plasma and total radioactivity in whole blood and plasma; (3) the absolute oral bioavailability of mitapivat; and (4) the metabolite profiles in plasma and excreta...
August 18, 2023: Clinical and Translational Science
https://read.qxmd.com/read/37594352/acquired-pseudoxanthoma-elasticum-like-syndrome-and-pyruvate-kinase-deficiency-a-case-of-iron-overload
#37
JOURNAL ARTICLE
Marine Robert, Séverine Audebert, Jean-Richard Eveillard, Frédéric Galacteros, Layal El Aridi, Le Flahec Glen, Clarisse Billon, Laurent Misery, Claire Abasq-Thomas
No abstract text is available yet for this article.
June 1, 2023: European Journal of Dermatology: EJD
https://read.qxmd.com/read/37589194/thiamine-metabolism-dysfunction-syndrome-5-thmd5-mimicking-acute-disseminated-encephalomyelitis
#38
Zachary E Thompson, Natalie K Boyd, Mellad M Khoshnood, Jonathan D Santoro
Thiamine pyrophosphate (TPP), the substrate of Thiamine pyrophosphate kinase (TPK), is an important cofactor in carbohydrate metabolism, specifically as a cofactor of the Pyruvate dehydrogenase complex (PDH) complex. The nervous system is particularly dependent on TPP due to its reliance on glucose metabolism. In this case, a four-year-old girl had a previously unreported pathogenic variant of the gene encoding TPK (TPK1) which presented as Thiamine metabolism dysfunction syndrome 5 (THMD5; OMIM 614458). She had been diagnosed with acute disseminated encephalomyelitis and autism spectrum disorder (ASD), and initially presented with fever and agitation following vaccinations...
December 2023: American Journal of Medical Genetics. Part A
https://read.qxmd.com/read/37588604/a-high-salt-diet-promotes-hypertrophic-scarring-through-trpc3-mediated-mitochondrial-ca-2-homeostasis-dysfunction
#39
JOURNAL ARTICLE
Weijie Xia, Qianran Wang, Shaoyang Lin, Yuanyuan Wang, Junbo Zhang, Hailin Wang, Xia Yang, Yingru Hu, Huaping Liang, Yuangang Lu, Zhiming Zhu, Daoyan Liu
Diet High in salt content have been associated with cardiovascular disease and chronic inflammation. We recently demonstrated that transient receptor potential canonical 3 (TRPC3) channels regulate myofibroblast transdifferentiation in hypertrophic scars. Here, we examined how high salt activation of TRPC3 participates in hypertrophic scarring during wound healing. In vitro, we confirmed that high salt increased the TRPC3 protein expression and the marker of myofibroblast alpha smooth muscle actin (α-SMA) in wild-type mice (WT) primary cultured dermal fibroblasts but not Trpc3 -/- mice...
August 2023: Heliyon
https://read.qxmd.com/read/37558589/a-stepwise-diagnostic-approach-for-undiagnosed-anemia-in-children-a-model-for-low-middle-income-country
#40
JOURNAL ARTICLE
Nihal Hussien Aly, Mohsen Saleh Elalfy, Safinaz Adel Elhabashy, Nadia Mohamed Mowafy, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Iman Ahmed Ragab
BACKGROUND: Reaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic studies, which makes undiagnosed anemia a unique clinical entity in tertiary hematology centers. In this study, we aim at plotting a stepwise diagnostic approach in children with undiagnosed anemia while identifying indications for genetic testing. PATIENTS AND METHODS: A one-year cross-sectional study involved 44 children and adolescents with undiagnosed anemia after undergoing an initial routine panel of investigations...
November 2023: Blood Cells, Molecules & Diseases
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